O'Brien attended Brookline High School, where he served as the managing editor of the school newspaper, The Sagamore. In his second year, O'Brien was an intern for Congressman Robert Drinan and in his senior year, he won the National Council of Teachers of English writing contest with his short story, "To Bury the Living". After graduating as valedictorian in 1981, he entered Harvard University. At Harvard, O'Brien lived in Holworthy Hall during his first year with Luis Ubiñas and two other roommates and Mather House during his three upper-class years. He concentrated in History & Literature, and graduated magna cum laude in 1985. O'Brien's senior thesis concerned the use of children as symbols in the works of William Faulkner and Flannery O'Connor. During college, O'Brien briefly served as the drummer in a band called "The Bad Clams", was a writer for the Harvard Lampoon humor magazine, and developed a spoof of the popular video game One on One: Dr. J vs. Larry Bird in which the Boston Celtics play against a classical ballet troupe. 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 school's newspaper The Harvard Crimson.