Padover was born in Vienna, Austria, and came to the United States at the age of fifteen in 1920, with his father, Keva Padover, an American citizen, and his mother, the former Frumet Goldmann. Padover earned his Bachelor of Arts degree from Wayne State University in Detroit., Michigan. From 1928-1929, he enrolled in graduate coursework at Yale University in New Haven, Connecticut. In 1930, he received a Master of Arts from and in 1932 a Ph.D. from the University of Chicago. Padover accepted research positions at the University of Chicago in 1932 and then a longer stint at the University of California at Berkeley. From 1938-1944, he worked in the United States Department of Interior during the long tenure of Secretary Harold L. Ickes. In 1944, Padover was a political analyst based in London for the Federal Communications Commission. He also served as an intelligence officer for the Office of Strategic Services, forerunner of the Central Intelligence Agency, and for the United States Army from 1944-1946. He served as an editorial writer from 1946-1948 for PM, a short-lived leftist New York City newspaper, In 1949, he joined the graduate faculty of The New School, where he remained until his death at the age of seventy-five.

In addition to the previously cited works, Padover penned several books about 20th century European and American politics, a memoir of his experiences as an intelligence officer, and several works on foreign policy. A liberal anti-communist Cold Warrior, Padover asserted during the 1950s that the former Soviet Union posed a serious threat to the security of the western world and must be carefully curtailed in its expansionist plans, the same idea ss George F. Kennan's containment. He also directed the General Seminar, the New School's interdisciplinary seminar for faculty colleagues.

Padover and Jacob W Landynski co-authored The Living U.S. Constitution, an examination of the forming of the United States Constitution, with character sketches of the delegates penned by their contemporaries. The book highlights the complete text of the Constitution and pertinent decisions of the United States Supreme Court affecting issues of constitutionality. Similar Padover works are The World of the Founding Fathers and Sources of Democracy: Voices of Freedom, Hope, and Justice.

On January 8, 1979, Padover wrote a column in Time Magazine entitled "Books: Marxist Mystery" in which he professed to examine Marx in the volume Karl Marx: An Intimate Biography from the viewpoint as neither a "True Believer" nor a "Great Hater". Padover said it had been difficult for historians to separate the history that made Marx as a philosophical thinker from the history created through Marxist ideas.

Padover's acclaimed Jefferson biography, Jefferson: A Great American's Life and Ideas, was first published in 1942, reprinted in 1952, and later released in an abridged edition.

Toward the end of his life, Padover contemplated writing a book about the American Council for Émigrés in the Professions, an organization committed to assisting refugees who fled from Nazi Germany and Austria. He procured physical possession of the ACEP files, housed them in his office at The New School, but died before he could complete the undertaking.