Adamic was born at Prapro?e Castle in Blato near Grosuplje, in what is now Slovenia (then part of the Austro-Hungarian Empire). The oldest son of a peasant family, he was given a limited childhood education at the city school and, in 1909, entered the primary school at Ljubljana. Early in his third year he joined a secret students' political club associated with the Yugoslav Nationalistic Movement that had recently sprung up in the South-Slavic provinces of Austria-Hungary. Swept up in a bloody demonstration in November 1913, Adamic was briefly jailed, expelled from school, and barred from any government educational institution. He was admitted to the Jesuit school in Ljubljana, but was unable to bring himself to go. "No more school for me. I was going to America," Adamic wrote. "I did not know how, but I knew that I would go."

On December 31, 1913, at the age of 14, Adamic emigrated to the United States. He finally settled in the Croatian fishing community of San Pedro, California. He became a naturalized United States citizen in 1918. At first he worked as a manual laborer and later at a Slovenian daily newspaper, Narodni Glas ("The Voice of the Nation"), that was published in New York. As an American soldier he participated in combat on the Western front during the First World War. After the war he worked as a journalist and professional writer.

All of Adamic's writings are based on his labor experiences in America and his former life in Slovenia. He achieved national acclaim in America in 1934 with his book The Native's Return, which was a bestseller directed against King Alexander's regime in the Kingdom of Yugoslavia. This book gave many Americans their first real knowledge of the Balkans. It contained many insights, but proved far from infallible: Adamic predicted that America would prosper by eventually "going left", i.e. turning socialist.

He received the Guggenheim Fellowship award in 1932. During the Second World War he had supported the Yugoslav National liberation struggle and the establishment of a socialist Yugoslav federation. He founded the United Committee of South-Slavic Americans in support of Marshall Tito. From 1949 he was a corresponding member of the Slovenian Academy of Sciences and Arts.

From 1940 onwards he served as editor of the magazine Common Ground. Adamic was the author of Dynamite: The Story of Class Violence in America (1931); Laughing in the Jungle: The Autobiography of an Immigrant in America (1932); The Native's Return: An American Immigrant Visits Yugoslavia and Discovers His Old Country (1934); Grandsons: A Story of American Lives (1935, novel); Cradle of Life: The Story of One Man's Beginnings (1936, novel); The House in Antigua (1937, novel); My America (1938); Two-Way Passage (1941); My Native Land (1943); Dinner at the White House (1946); and The Eagle and the Root (1950).

Plagued by failing health, he is believed to have shot himself at his residence in Milford, New Jersey. He died at a time of political tension and intrigue in Yugoslavia, and there was press speculation in America that his death might have been an assassination by some Balkan faction, but no definitive proof of this theory has ever surfaced.

According to John McAleer's Edgar Award-winning Rex Stout: A Biography (1977), it was the influence of Adamic that led Rex Stout to make his fictional detective Nero Wolfe a native of Montenegro, in what was then Yugoslavia. Stout and Adamic were friends and frequent political allies, and Stout expressed uncertainty to McAleer about the circumstances of Adamic's death. In any case, the demise seems to have inspired Stout's 1954 novel The Black Mountain, in which Nero Wolfe returns to his homeland to hunt down the killers of an old friend.

Adamic told The Literary Digest: "My name is pronounced in this country (America) exactly as the word Adamic, pertaining to Adam": a-dam'ik. (Charles Earle Funk, What's the Name, Please?, Funk & Wagnalls, 1936.) His original surname was Adami?, pronounced in Slovenian a-DAH-mich.