Bernard Lewis was born to middle-class Jewish parents in Stoke Newington, London. He became interested in languages and history while preparing for his bar mitzvah.

Lewis graduated in 1936 from the School of Oriental Studies (now SOAS, School of Oriental and African Studies) at the University of London with a B.A. in History with special reference to the Near and Middle East, and obtaining his Ph.D. three years later, also from SOAS, specializing in the History of Islam. Lewis also studied law, going part of the way toward becoming a solicitor, but returned to study Middle Eastern history. He undertook post-graduate studies at the University of Paris, where he studied with the orientalist Louis Massignon and earned the "Diplôme des Études Sémitiques" in 1937.He returned to SOAS in 1938 as an assistant lecturer in Islamic History.

During the Second World War, Lewis served in the British Army in the Royal Armoured Corps and Intelligence Corps in 1940—41, before being seconded to the Foreign Office. After the war, he returned to SOAS, and in 1949, at the age of 33, he was appointed to the new chair in Near and Middle Eastern History.

In 1974, aged 57, Lewis accepted a joint position at Princeton University and the Institute for Advanced Study, also located in Princeton, New Jersey. The terms of his appointment were such that Lewis taught only one semester per year, and being free from administrative responsibilities, he could devote more time to research than previously. Consequently, Lewis's arrival at Princeton marked the beginning of the most prolific period in his research career during which he published numerous books and articles based on the previously accumulated materials. In addition, it was in the U.S. that Lewis became a public intellectual. Upon his retirement from Princeton in 1986, Lewis served at Cornell University until 1990.

Lewis has been a naturalized citizen of the United States since 1982. He married Ruth Hélène Oppenhejm in 1947 with whom he had a daughter and a son before the marriage was dissolved in 1974.

In 1966, Lewis was a founding member of the learned society, Middle East Studies Association of North America (MESA), but in 2007, he broke away and founded Association for the Study of the Middle East and Africa (ASMEA) to challenge MESA, which the New York Sun noted as "dominated by academics who have been critical of Israel and of America's role in the Middle East." The organization was formed as an academic society dedicated to promoting the highest standards of research and teaching in Middle Eastern and African studies, and related fields, with Lewis as Chairman of its academic council.

In 1990 the National Endowment for the Humanities selected Lewis for the Jefferson Lecture, the U.S. federal government's highest honor for achievement in the humanities. His lecture, entitled "Western Civilization: A View from the East," was revised and reprinted in The Atlantic Monthly under the title "The Roots of Muslim Rage." His 2007 Irving Kristol Lecture, given to the American Enterprise Institute, was published as Europe and Islam.

Lewis' influence extends beyond the academe to the general public. He is a pioneer of the social and economic history of the Middle East and is famous for his extensive research of the Ottoman archives. He began his research career with the study of medieval Arab, especially Syrian, history. His first article, dedicated to professional guilds of medieval Islam, had been widely regarded as the most authoritative work on the subject for about thirty years.However, after the establishment of the state of Israel in 1948, scholars of Jewish origin found it more and more difficult to conduct archival and field research in the Arab countries where they were suspected of espionage. Therefore, Lewis switched to the study of the Ottoman Empire, while continuing to research Arab history through the Ottoman archives, which had only recently been opened to Western researchers. A series of articles that Lewis published over the next several years revolutionized the history of the Middle East by giving a broad picture of Islamic society, including its government, economy, and demographics.

Lewis argues that the Middle East is currently backward and its decline was a largely self-inflicted condition resulting from both culture and religion, as opposed to the post-colonialist view which posits the problems of the region as economic and political maldevelopment mainly due to the 19th century European colonization. In his 1982 work Muslim Discovery of Europe, Lewis argues that Muslim societies could not keep pace with the West and that "Crusader successes were due in no small part to Muslim weakness." Further, he suggested that as early as the 11th century Islamic societies were decaying, primarily the byproduct of internal problems like "cultural arrogance," which was a barrier to creative borrowing, rather than external pressures like the Crusades.

In the wake of Soviet and Arab attempts to delegitimize Israel as a racist country, Lewis wrote a study of anti-Semitism, Semites and Anti-Semites (1986). In other works he argued Arab rage against Israel was disproportionate to other tragedies or injustices in the Muslim world: the Soviet invasion of Afghanistan and control of Muslim-majority land in Central Asia, the bloody and destructive fighting during the Hama uprising in Syria (1982), the Algerian civil war (1992—98), and the Iran-Iraq War (1980—88).

In addition to his scholarly works, Lewis wrote several influential books accessible to the general public: The Arabs in History (1950), The Middle East and the West (1964), and The Middle East (1995). In the wake of the September 11, 2001 attacks, the interest in Lewis's work surged, especially his 1990 essay The Roots of Muslim Rage. Three of his books were published after 9/11: What Went Wrong? (written before the attacks), which explored the reasons of the Muslim world's apprehension (and sometimes outright hostility) to the modernization, and The Crisis of Islam, and Islam: The Religion and the People (published in 2009).

In the mid-1960s, Lewis emerged as a commentator on the issues of the modern Middle East, and his analysis of the Israeli-Palestinian conflict and the rise of militant Islam brought him publicity and aroused significant controversy. American historian Joel Beinin has called him "perhaps the most articulate and learned Zionist advocate in the North American Middle East academic community ..." Lewis's policy advice has particular weight thanks to this scholarly authority. U.S. Vice President Dick Cheney remarked: "...in this new century, his wisdom is sought daily by policymakers, diplomats, fellow academics, and the news media."

A harsh critic of the Soviet Union, Lewis continues the liberal tradition in Islamic historical studies. Although his early Marxist views had a bearing on his first book The Origins of Ismailism, Lewis subsequently discarded Marxism. His later works are a reaction against the left-wing current of Third-worldism, which came to be a significant current in Middle Eastern studies.

Lewis advocates closer Western ties with Israel and Turkey, which he saw as especially important in light of the extension of the Soviet influence in the Middle East. Modern Turkey holds a special place in Lewis's view of the region due to the country's efforts to become a part of the West. He is a Honorary Fellow of the Institute of Turkish Studies, an honor which is given "on the basis of generally recognized scholarly distinction and... long and devoted service to the field of Turkish Studies."

Lewis views Christendom and Islam as civilizations that have been in perpetual collision since the advent of Islam in the 7th century. In his essay The Roots of Muslim Rage (1990), he argued that the struggle between the West and Islam was gathering strength. According to one source, this essay (and Lewis' 1990 Jefferson Lecture on which the article was based) first introduced the term "Islamic fundamentalism" to North America. This essay has been credited with coining the phrase "clash of civilizations", which received prominence in the eponymous book by Samuel Huntington. However, another source indicates that Lewis first used the phrase "clash of civilizations" at a meeting in Washington in 1957 where it is recorded in the transcript.

In 1998, Lewis read in a London-based newspaper Al-Quds Al-Arabi a declaration of war on the United States by Osama bin Laden. In his essay "A License to Kill", Lewis indicated he considered bin Laden's language as the "ideology of jihad" and warned that bin Laden would be a danger to the West. The essay was published after the Clinton administration and the US intelligence community had begun its hunt for bin Laden in Sudan and then in Afghanistan.

In August 2006, in an article about whether the world can rely on the concept of mutual assured destruction as a deterrent in its dealings with Iran, Lewis wrote in the Wall Street Journal about the significance of August 22, 2006 in the Islamic calendar. The Iranian president had indicated he would respond by that date to U.S. demands regarding Iran's development of nuclear power; Lewis wrote that the date corresponded to the 27th day of the month of Rajab of the year 1427, the day Muslims commemorate the night flight of the prophet Muhammad from Jerusalem to heaven and back. Lewis wrote that it would be "an appropriate date for the apocalyptic ending of Israel and, if necessary, of the world." The article received significant press coverage though the day passed without any incident.

Lewis is known for his literary sparrings with Edward W. Said, the Palestinian-American literary theorist whose aim was to deconstruct what he called Orientalist scholarship. Said, a professor at Columbia University, characterised Lewis's work as a prime example of Orientalism in his 1978 book Orientalism. Said asserted that the field of Orientalism was political intellectualism bent on self-affirmation rather than objective study, a form of racism, and a tool of imperialist domination. He further questioned the scientific neutrality of some leading Middle East scholars such as Bernard Lewis on the Arab world. In an interview with Al-Ahram Weekly, Said suggested that Lewis' knowledge of the Middle East was so biased it could not be taken seriously, and claimed "Bernard Lewis hasn't set foot in the Middle East, in the Arab world, for at least 40 years. He knows something about Turkey, I'm told, but he knows nothing about the Arab world."

Edward Said considered that Lewis treats Islam as a monolithic entity without the nuance of its plurality, internal dynamics, and historical complexities, and accused him of "demagogy and downright ignorance."

Rejecting the view that western scholarship was biased against the Middle East, Lewis responded that Orientalism developed as a facet of European humanism, independently of the past European imperial expansion. He noted the French and English pursued the study of Islam in the 16th and 17th centuries, yet not in an organized way, but long before they had any control or hope of control in the Middle East; and that much of Orientalist study did nothing to advance the cause of imperialism. "What imperial purpose was served by deciphering the ancient Egyptian language, for example, and then restoring to the Egyptians knowledge of and pride in their forgotten, ancient past?"

The first two editions of Lewis' The Emergence of Modern Turkey (1961 and 1968) describe the Armenian massacres of WWI as "the terrible holocaust of 1915, when a million and a half Armenians perished". In later editions, this text is altered to: "the terrible slaughter of 1915, when, according to estimates, more than a million Armenians perished, as well as an unknown number of Turks." Lewis was later one of 69 scholars to co-sign a 1985 petition asking the US Congress to avoid a resolution condemning the events as "genocide".

The change in Lewis' textual description of the Armenian massacres, and his signing of the petition against the Congressional resolution, was controversial among some historians and journalists, who suggested that Lewis was engaging in historical revisionism to serve his own political and personal interests. The original text had already drawn criticism for what some historians believe to be its exaggeration of unity and strength among Armenians: "[Lewis] implies that both had equal military and political force at their disposal to defend their interests. The fact is that the Armenians had neither a police force nor an army".

Lewis later called the label "genocide" the "Armenian version of this history" in a November 1993 Le Monde article, for which he faced a civil proceeding in a French court. He was ordered to pay one franc as damages for his statements on the Armenian Genocide in Ottoman Turkey. Lewis has stated that while mass murders did occur, he did not believe there was sufficient evidence to conclude it was government-sponsored, ordered or controlled and therefore did not constitute genocide. The court stated that "by concealing elements contrary to his opinion, he neglected his duties of objectivity and prudence". This sentence was criticized as liberticide by some historians and media outlets. Three other court cases against Bernard Lewis failed in Paris tribunal, including one filed by the Armenian National Committee of France and two filed by Jacques Trémolet de Villers.

When Lewis received the National Humanities Medal from US President George W. Bush in November 2006, the Armenian National Committee of America objected: "The President's decision to honor the work of a known genocide denier ... an academic mercenary whose politically motivated efforts to cover up the truth run counter to the very principles this award was established to honor ... represents a true betrayal of the public trust."

Lewis' views on the Armenian Genocide were criticized by a number of historians and sociologists. Stephen Zunes described Lewis as a "notorious genocide-denier", and Yair Auron suggested that "Lewis’ stature provided a lofty cover for the Turkish national agenda of obfuscating academic research on the Armenian Genocide". Israel Charny wrote that Lewis' "seemingly scholarly concern... of Armenians constituting a threat to the Turks as a rebellious force who together with the Russians threatened the Ottoman Empire, and the insistence that only a policy of deportations was executed, barely conceal the fact that the organized deportations constituted systematic mass murder". Charny compares the "logical structures" employed by Lewis in his denial of the genocide to those employed by Ernst Nolte in his Holocaust negationism.

In response, Lewis argued that:

Lewis stated that he believed "to make [the Armenian Genocide], a parallel with the Holocaust in Germany" was "rather absurd." In an interview with Ha'aretz he stated:

Some other commentators have been more sympathetic to Bernard Lewis' views, or adopted them themselves.

In a 2002 interview with the Canadian Broadcasting Corporation's "Hot Type" program, linguist and political activist Noam Chomsky detailed a series of comments from a declassified Eisenhower Administration memo:

Chomsky claimed that Bernard Lewis omitted  evidence of Western culpability for failures in the region.

Lewis responded:

It has been alleged that Lewis is "perhaps the most significant intellectual influence behind the invasion of Iraq". Others have attributed to him the view that regime change in Iraq would provide a jolt that would "modernize the Middle East". Critics of Lewis have suggested that Lewis' allegedly 'Orientalist' theories about "What Went Wrong" in the Middle East, and other important works, formed the intellectual basis of the push towards war in Iraq.

Lewis does not advocate imposing freedom and democracy on Islamic nations."There are things you can't impose. Freedom, for example. Or democracy. Democracy is a very strong medicine which has to be administered to the patient in small, gradually increasing doses. Otherwise, you risk killing the patient. In the main, the Muslims have to do it themselves."

Ian Buruma, writing for The New Yorker in an article subtitled "The two minds of Bernard Lewis", finds Lewis's stance on the war difficult to reconcile with Lewis's past statements cautioning democracy's enforcement in the world at large. Buruma ultimately rejects suggestions by his peers that Lewis promotes war with Iraq to safeguard Israel, but instead concludes "perhaps he (Lewis) loves it (the Arab world) too much":

In 2006, Lewis wrote that Iran had been working on a nuclear weapon for fifteen years. According to Lewis, mutual assured destruction is not an effective deterrent in the case of Iran, because of what Lewis describes as the Iranian leadership's "apocalyptic worldview" and the "suicide or martyrdom complex that plagues parts of the Islamic world today". He then suggests the possibility of a nuclear strike on Israel on August 22, 2006:

Juan Cole responded that there was no evidence to suggest that Iran "had been working assiduously on a nuclear weapon for fifteen years". He also takes issue with Lewis' suggestion that Ahmedinejad "might deploy this weapon against Israel on August 22, 2006":