Carey was working as a stand-up comedian in 1991 when he appeared on The Tonight Show Starring Johnny Carson. His performance that night brought the house down and impressed Johnny Carson personally. Carey claims he reached the limit on his credit card the next day returning calls from interested casting directors, and he credited Carson with making his career. He subsequently appeared in a number of supporting roles on television shows, some them alongside Kathy Kinney, in which he developed the character of a hapless middle-class bachelor. In 1995 ABC began showing The Drew Carey Show, a sitcom that featured Carey and Kinney in their previous characters. Carey played the assistant director of personnel at a department store in Cleveland, Ohio. Carey also hosted the United States version of the improvisational comedy show, Whose Line Is It Anyway?

In 1997, Carey published his autobiography, entitled Dirty Jokes and Beer: Stories of the Unrefined, where he shared memories of his early childhood, how his father died when Drew was eight years old, his revelation that he was once sexually molested, his bouts with depression, his failed attempts at suicide, his college fraternity years while attending Kent State University, and his professional career up to that time.

In 2000, he received an honorary Ph.D. degree from Cleveland State University.

Carey was the first TV star (as opposed to wrestler or athlete) to ever enter the World Wrestling Federation's 30-man "Royal Rumble" battle royal match in 2001; he was promoting an improv comedy pay per view at the time. He appeared in a few backstage segments before his brief participation in the match; he eliminated himself by offering a bribe and then fleeing the ring when Kane came out.

Drew Carey is also known for his Republican leanings and has expressed support for the Libertarian Party. The Drew Carey Show often supported a libertarian critique of political correctness, government regulations, racism and sexism and anti-gay bias with Carey's cross-dressing brother, Drew dating a bisexual woman (played by Illeana Douglas) for two episodes, an ongoing storyline that was critical of the Boy Scouts of America exclusionary policy against gay men, and supportive of same-sex marriage. Since the show was cancelled, however, Drew has clarified that he is more of a conservative with libertarian leanings, and that he said he was libertarian to avoid a Hollywood bias against conservatives.

For The WB's 2004-2005 prime time schedule, Carey co-produced and starred in Drew Carey's Green Screen Show, a spin-off of Whose Line Is It Anyway. It was cancelled by the WB, but picked up shortly afterward by Comedy Central.

Philanthrophically, Carey is known for his support of libraries. On May 2, 2000, in a celebrity edition of Who Wants To Be A Millionaire?, he selected the Ohio Library Foundation to receive his $500,000 earnings. He credits libraries for launching his comedy career. After he left the Reserve, he followed up on a suggestion by a friend that he go into comedy by checking out books on how to write jokes from the library.

Carey is also known for being a devoted Cleveland Browns, Indians and US Soccer fan. When he promoted The Drew Carey Show in 1995, at the same time the Indians were making a miraculous run at the World Series, he poked fun at the rest of baseball by saying, "Finally, it's your team that sucks!" He is also credited as being a fan of the Scottish soccer team Rangers F.C.. He is also a season ticket holder with the Los Angeles Galaxy.

Comedy Central ranked him number 84 on its list of the 100 greatest standups of all time.

Drew has also made a cameo appearance in the game The Sims, but only in the House Party expansion pack. To make him appear, your Sims must throw a successful party, which will cause a limo to show up and Drew will join the festivities. Drew is a fan of The Sims series, and has been said to play it often. During one April Fool's episode of The Drew Carey Show, a scene takes place completely within The Sims. He also loves playing RuneScape.

Drew also has played on the World Poker Tour in the Hollywood Home games for The Cleveland Public Library charity.

You can sometimes see Drew Carey on the sidelines of US National Team soccer games as a press photographer . His images are sold via wire services under a pseudonym.

Councilman Sean Brenna of Parma, Ohio has commended Carey for placing Parma (a Cleveland suburb) on the world stage.

Carey has had refractive surgery to correct his vision and therefore does not actually require glasses. Any glasses he wears in public are merely props to help the audience recognize him.