Conan Christopher O'Brien was born on April 18, 1963, in the Boston suburb of Brookline, Mass. He was the third of six children born to Ruth and Thomas O'Brien. His mother was a lawyer; his father practiced medicine and taught at Harvard Medical School. Conan was named for an early Gaelic religious figure, and he described his family as “extremely Irish.”

Young Conan displayed an early interest in entertaining and comedy. He took tap dancing lessons and wrote comedic plays as a child. The first time he stood before an audience and told jokes was at his high school graduation, for which he acted as a host.

In 1981 O'Brien began studies at Harvard University, where he majored in American history and literature. He devoted most of his time to the Harvard Lampoon, a prestigious humor magazine. O'Brien wrote for the Lampoon during all four years he attended Harvard and was elected president of the magazine for an unprecedented two consecutive terms in 1983–84. O'Brien graduated magna cum laude from Harvard in 1985.

After graduation, O'Brien moved to Los Angeles to join the writing team for the cable television network HBO's popular parody of a news show, Not Necessarily the News. He wrote for the show for two years and acted in several improvisational groups, including the Groundlings. O'Brien also acted in some small films during this period.

In 1988 O'Brien joined the Fox network's Wilton North Report, a late-night comedy show that aired for only four weeks. He then acted onstage in the ‘Happy Happy Good Show' in Chicago and Los Angeles. That same year Saturday Night Live hired O'Brien. He wrote for the late-night variety show for three and a half years and was responsible for such popular recurring characters as Mr. Short-Term Memory and The Girl Watchers, played by Tom Hanks and Jon Lovitz. In 1989, O'Brien and other Saturday Night Live writers won an Emmy award.

After leaving Saturday Night Live in 1991, O'Brien wrote and produced a television pilot called Lookwell which was not picked up as a series. He then joined the writing staff of The Simpsons, a popular cartoon about a wacky suburban family. O'Brien's combination of satire and goofiness contributed greatly to the success of such episodes as “Marge vs. the Monorail,” “Homer Goes to College,” and “Wacking Day.” O'Brien eventually became the show's supervising producer.

O'Brien's biggest break came in 1993, when David Letterman told NBC that he was taking his late-night talk show to rival network CBS. NBC asked several prominent television personalities to take over the show, but all declined. Saturday Night Live producer Lorne Michaels then suggested that O'Brien audition for the job. On April 26, 1993, the announcement was made: Conan O'Brien would be the new late-night host.

Considering his lack of experience behind the camera and relative obscurity to the viewing public, it was an amazing stroke of luck for the 29-year-old. The opportunity also brought a wave of media scrutiny, however. Inevitably compared to Letterman, O'Brien's inexperience and nervousness in his new role showed on camera. Critics panned the show and NBC doled out 13-week contracts one at a time, keeping the entertainment rumor mill flowing with talk of imminent cancellation.

However, O'Brien was determined not to flop, and with time began to develop a very devoted audience, primarily made up of college-age youth. Late Night with Conan O'Brien had the traditional look of a late-night talk show, with O'Brien behind a desk, a sidekick, Andy Richter, helping his jokes along, and a hip band, the Max Weinberg 7, playing in the background. But O'Brien was more irreverent and silly than Jay Leno or even David Letterman, and he aimed his material squarely at the 18- to 34-year-old market, mixing in such zany recurring comedy bits as “Andy & Conan Taking the Desk for a Drive,” “Audience Hygiene,” “Classic Films Dubbed by Children,” and “Clutch Cargo,” in which O'Brien “interviewed” celebrities whose images appeared on a screen with moving lips superimposed.

By 1997 the 6-foot 4-inch (1.93-meter) redheaded entertainer had secured a longer contract from NBC and had written a book called ‘If They Mated', which featured computer-generated predictions of what celebrities' children would look like.