Wilentz was born on February 20, 1951 in New York City, where his father Eli  and uncle Ted  owned a well-known Greenwich Village bookstore, the Eighth Street Bookshop. Wilentz earned one B.A. at Columbia University in 1972, before earning another at Oxford University (Balliol College) in 1974 on a Kellett Fellowship. In 1975 he earned an M.A. at Yale University and in 1980 he received his Ph.D. also from Yale, under the supervision of David Brion Davis.
Wilentz' historical scholarship has focused on the importance of class and race in the early national period, especially in New York City. Wilentz has also co-authored books on nineteenth-century religion and working-class life. His highly detailed The Rise of American Democracy: Jefferson to Lincoln (W.W. Norton, 2005) won the Bancroft Prize. His goal was to revive the reputation of Andrew Jackson and Jacksonian Democracy, which was under attack from the left because of Jackson's support for slavery and pursuit of escaped slaves, and especially his harshness toward Indians, including his forced removals of Indian populations from land confiscated by European-ancestry populations. Wilentz returned to the pro-Jackson themes of Arthur Schlesinger Jr., who in 1946 had hailed the pro-labor policies of Northern, urban Jacksonians.
He has more recently turned his scholarship to modern U.S. history, notably in The Age of Reagan: A History, 1974–2008, published in May 2008.
Columbia professor Eric Foner, a long-time friend, says Wilentz "has written some of the very best examples of the avant-garde of the 70s and the avant-garde more recently. Back then we were trying to recover a lost past or neglected past. More recently historians have been trying to integrate that vision into a larger vision of American history as a whole."
A contributing editor at The New Republic, Wilentz has written about about music and the arts, as well as history and politics. He received a Grammy nomination, and a 2005 ASCAP Deems Taylor Award for the liner notes Wilentz contributed to the album The Bootleg Series Vol. 6: Bob Dylan Live 1964, Concert at Philharmonic Hall. In 2010, Wilentz published his study, Bob Dylan In America, placing Dylan in the context of American 20th century history and culture. The book contained essays on Dylan's relationship to Aaron Copland, Allen Ginsberg and the Beat generation, and the recording of Blonde on Blonde.
Wilentz has prominently engaged in current politics. Wilentz was reportedly a long-time family friend of the Clintons. He appeared in contemporary politics, as a staunch defender of Bill Clinton and Hillary Clinton: he appeared before the House Judiciary Committee on December 8, 1998 to argue against the Clinton impeachment. He told the House members that, if they voted for impeachment but were not convinced Clinton's offenses were impeachable:
"...history will track you down and condemn you for your cravenness."
In 2006, he wrote an article denouncing the George W. Bush presidency, titled "The Worst President in History?"  which appeared in Rolling Stone magazine. The article received an immediate national response from conservatives; National Review attacked Wilentz's analysis as "blinkered" and called him "the modern Arthur Schlesinger Jr."
Wilentz followed up during the 2008 general election with another article in Rolling Stone, describing how the failures of the Bush administration had caused a "political meltdown" of the Republican Party, with potentially enormous long-term effects. In the wake of the October, 2013 federal government shutdown, Wilentz authored another article in Rolling Stone on what he called a "crisis" within the Republican Party with its gradual descent into extremism.
In 2008 Wilentz was an outspoken supporter of Sen. Hillary Clinton. He wrote an essay in the New Republic analyzing Sen. Barack Obama's campaign, charging Obama with creating "manipulative illusion[s]" and "distortions," and having "purposefully polluted the [primary electoral] contest" with "the most outrageous deployment of racial politics since the Willie Horton ad campaign in 1988." During the Democratic National Convention, Wilentz charged in Newsweek that "liberal intellectuals have largely abdicated their responsibility to provide unblinking and rigorous analysis" of Obama. "Hardly any prominent liberal thinkers" have questioned his "rationalizations" about his relationship to his former pastor, the Rev. Jeremiah Wright Jr., or "his patently evasive accounts" of his "ties" to the "unrepentant terrorist William Ayers." For Wilentz, Obama is untested, cloudy, problematic—and liberal intellectuals have given him a free ride. Wilentz was criticized by bloggers and others for his criticism of Obama. He has also come under fire for the alleged historical inaccuracy of his attacks on the idea of nullification.
In January 2014 Wilentz took issue with those involved in the 2013 NSA leaks, in particular Edward Snowden, Glenn Greenwald, and Julian Assange. In Wilentz' view, "the value of some of their revelations does not mean that they deserve the prestige and influence that has been accorded to them. The leakers and their supporters would never hand the state modern surveillance powers, even if they came wrapped in all sorts of rules and regulations that would constrain their abuse. They are right to worry, but wrong — even paranoid — to distrust democratic governments in this way. Surveillance and secrecy will never be attractive features of a democratic government, but they are not inimical to it, either. This the leakers will never understand."
- 1984 Beveridge Award from the American Historical Association for Chants Democratic: New York City and the Rise of the American Working Class, 1788–1850
- 2006 Bancroft Prize for The Rise of American Democracy: Jefferson to Lincoln
- "On Class and Politics in Jacksonian America," Reviews in American History, Vol. 10, No. 4, The Promise of American History: Progress and Prospects (Dec., 1982), pp. 45–63 in JSTOR
- "Against Exceptionalism: Class Consciousness and the American Labor Movement, 1790-1920," International Labor and Working Class History, 26 (Fall 1984): 1–24,
- Chants Democratic: New York City and the Rise of the American Working Class, 1788–1850 (1984)
- Merrill, Michael, and Sean Wilentz, eds. The Key of Liberty: The Life and Democratic Writings of William Manning, "A Laborer," 1747–1814 (1993)
- Johnson, Paul E., and Sean Wilentz. The Kingdom of Matthias. (1994) excerpt and text search
- Andrew Jackson (2005) excerpt and text search
- The Rise of American Democracy: Jefferson to Lincoln (2005) excerpt and text search
- Wilentz, Sean and Greil Marcus, eds. Rose and the Briar: Death, Love and Liberty in the American Ballad (2005)
- Wilentz, Sean, and Jonathan Earle, eds. Major Problems in the Early Republic (1992; 2nd ed. 2007)
- The Age of Reagan: A History, 1974–2008 (2008) excerpt and text search
- Bob Dylan in America, 1st ed., New York : Doubleday, 2010. ISBN 978-0-385-52988-4
- President Ulysses S. Grant and the Battle for Equality from Profiles in Leadership (2011) W. W. Norton & Company
- Altschuler, Glenn C. "Democracy as a Work in Progress," Reviews in American History, Volume 34, Number 2, June 2006, pp. 169–175 in Project Muse, review of The Rise of American Democracy: Jefferson to Lincoln
- John Ehrman, "There He Goes Again: A review of The Age of Reagan: A History, 1974-2008, Sean Wilentz" The Claremont Institute (2008), review by conservative scholar
- "Wilentz webpage at Princeton University, Department of History". Princeton.edu. 2010-01-15. Retrieved 2010-08-13.
- Thomas, Robert McG., Jr., "Eli Wilentz, Whose Bookstore Lured the 'Beats,' Is Dead at 76", The New York Times, June 26, 1995
- Martin, Douglas, "Theodore Wilentz, 86, Dies; A Bookman Extraordinaire", The New York Times, May 6, 2001
- Reed, Bill, "Positively Eighth Street", Reality Studio
- quoted in Christopher Shea, "Sean Wilentz, Bringing It All Back Home; With a new book on Bob Dylan, the historian again defies expectations," The Chronicle Review Sept 5, 2010
- Pallen (2004-12-09). "Wilentz receives Grammy nomination". Princeton University. Retrieved 2010-07-20.
- ASCAP, "2005 Deems Taylor Award Winners"
- Dyer, Geoff (September 12, 2010). "Bob Dylan in America by Sean Wilentz". The Observer/Guardian. Retrieved January 24, 2014.
- Christine Stansell website at the University of Chicago History Department
- "The Charisma Mandate" The New York Times
- "Immobilizing Lies", The New York Times, 1998-09-12
- "The Worst President in History? One of America's leading historians assesses George W. Bush", Rolling Stone, 2006-04-21
- "Sean Wilentz is the Modern Arthur Schlesinger Jr." National Review, 2006-05-22
- "How Bush Destroyed the Republican Party Rolling Stone, 2008-09-04
- Sean Wilentz, Rolling Stone, October 10, 2013, "Republican Extremism and the Lessons of History", Retrieved October 31, 2013
- "Making the Case... for Hillary Clinton", by Sean Wilentz, Newsweek.com, 2007-11-16
- "Race Man", by Sean Wilentz, The New Republic, 2008-02-27
- Sean Wilentz, "A Liberal's Lament," Newsweek issue of Sept. 1, 2008, online
- Russell Jacoby, "Sean Wilentz, Out on a Partisan Limb," Chronicle of Higher Education issue dated September 19, 2008 online
- Thomas Woods, Jr., The Ivy League Hates Nullification, LewRockwell.com (2010-04-06)
- Sean Wilentz (19 January 2014), Would You Feel Differently About Snowden, Greenwald, and Assange If You Knew What They Really Thought? The New Republic
- Wilentz interview from 2005
- Wilentz interview NPR 2010
- C-SPAN Q&A interview with Wilentz, May 7, 2006