O'Brien was born in Brookline, Massachusetts, a suburb of Boston, the son of Ruth (née Reardon), an attorney and partner at the Boston firm of Ropes & Gray,and Thomas O'Brien, a physician, epidemiologist and professor of medicine at Harvard.He is the third of six children. O'Brien's family was Irish Catholic and descended from pre-Civil War era immigrants;In a Late Night episode, O'Brien paid a visit to County Kerry, Ireland, where his ancestors originated.O'Brien attended Brookline High School, where he served as the managing editor of the school newspaper.In his senior year, O'Brien won the National Council of Teachers of English writing contest with his short story "To Bury the Living."[8] After graduating as valedictorian in 1981, he entered Harvard University.At Harvard, O'Brien lived in Holworthy Hall during his freshman year, and Mather House during his three upper-class years. His major was in History.
His senior thesis concerned the use of children as symbols in the works of William Faulkner and Flannery O'Connor.Throughout college, O'Brien was a writer for the Harvard Lampoon humor magazine. He also briefly served as the drummer in a band called "The Bad Clams".
During his sophomore and junior years, he served as the Lampoon's president.At this time, O'Brien's future boss at NBC, Jeff Zucker was serving as President of the rival The Harvard Crimson.
