Carey is the youngest of Lewis and Beulah Carey's three sons and raised in the Old Brooklyn neighborhood of Cleveland, Ohio. When Drew was eight years old, his father died from a brain tumor. He played the cornet and trumpet in the marching band of James Ford Rhodes High School, from which he graduated in 1975.

He continued on to college at Kent State University (KSU) and was a part of Delta Tau Delta Fraternity. He was expelled twice for poor academic performance. He left KSU after three years. After leaving the university, Carey enlisted into the United States Marine Corps Reserve in 1980 and served for six years. He moved to Las Vegas for a few months in 1983, and for a short time worked as a bank Teller and a waiter at Denny's.

In 1985, he began his comedy career by following up on a suggestion by David Lawrence (a disc jockey friend who had been paying Drew to write jokes for David's radio show in Cleveland) to go to the library and borrow books on how to write jokes. The following year, after winning an open-microphone contest, he became Master of Ceremonies at the Cleveland Comedy Club. He performed at comedy clubs over the next few years in Cleveland and Los Angeles. He first came to the national eye as a Comedian when he competed in the 1988 Star Search. Carey was working as a stand-up Comedian when he appeared on The Tonight Show Starring Johnny Carson in November 1991. His performance that night impressed Carson, who invited Carey to the couch next to his desk; this was considered a rare honor for any Comedian. In that same year, Carey joined the 14th Annual Young Comedians Special on HBO and made his first appearance on Late Night with David Letterman. In 1994, Carey wrote his own stand-up comedy special, Drew Carey: Human Cartoon, which aired on Showtime and won a CableACE Award for Best Writing.

Carey began appearing in commercials for restaurants in the late 1990s in Canada with The Great Root Bear, but his two-year contract with A&W Food Services of Canada was cut short in November 1998 after an episode of The Drew Carey Show featured McDonald's. As a result of his dismissal, Carey sued A&W for compensation.

Although primarily known for his television work, Carey has done limited film work, with his first appearance in 1993's Coneheads. His next film was the 2000 television film Geppetto, which debuted on The Wonderful World of Disney. The film, an adaptation of Pinocchio, included actor Wayne Brady, who had joined Carey on his improv shows. Carey took singing lessons to prepare for the role. In 2005, Carey appeared in three films: the animated film Robots, where he provided a voice-over for the character Crank; The Aristocrats, where he retold a dirty joke along with other celebrities; and the documentary Fuck, where he was interviewed.

After their stint on Someone Like Me, Carey and Helford developed and produced the storyline for The Drew Carey Show. The sitcom revolved around a fictionalized version of Carey, as he took on the stresses of life and work with his group of childhood friends. The show premiered on September 13, 1995 on ABC. In his autobiography, Carey revealed his frustration with having to deal with censors and being unable to employ the off-color humor Common in his stand-up routines. Carey initially earned $60,000 per episode in the first seasons, then renegotiated for $300,000. By the final season, he was earning $750,000 per episode. The show had high ratings for its first few seasons, but declining ratings and increasing production costs (around $3 million per episode) precipitated its cancellation. The program had a total of 233 episodes over its nine-year run, and Carey was one of four actors to appear in every episode.

Carey has routinely written throughout his career, including developing his stand-up comedy routines in his early stand-up career, and then moving on to assist in writing sitcoms. In 1997, Carey published his autobiography, Dirty Jokes and Beer: Stories of the Unrefined, wherein he shared memories of his early childhood and of his father's death when he was eight. He also revealed that he was once molested, had suffered bouts of depression, and had made two suicide attempts by swallowing a large amount of sleeping pills. The book discusses his college fraternity years while attending Kent State University and his professional career up to that time. The book featured large amounts of profanity and, as the title suggests, includes multiple dirty jokes (there is one at the start of each chapter) and references to beer, which was a departure from his on-screen persona. The book was featured on The New York Times bestseller list for three months.

While still starring in The Drew Carey Show, Carey began hosting the American version of the improvisational comedy show Whose Line Is It Anyway? in 1998. He would announce the improv guests, direct the games, and then would usually involve himself in the final game of the episode. The show ran for a total of 220 episodes until the show's cancellation in 2006. In 1998, the New York Friars' Club made Carey the newest inductee of the group's Comedy Central Roast. His friend Ryan Stiles (who costarred in The Drew Carey Show and Whose Line Is It Anyway?) served as the roastmaster. Carey's income from Whose Line Is It Anyway? and The Drew Carey Show led to his inclusion on the Forbes list of highest-paid entertainers of 1998, at 24th with $45.5 million.

Also in 1999, Carey appeared in "Weird Al" Yankovic's music video for his song "It's All About The Pentiums".

Carey is a supporter of libraries, crediting them for beginning his successful comedy career. 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 winnings. He later went on to win an additional $32,000 on the second Celebrity Millionaire, making him one of the biggest winning contestants on Millionaire who did not win the top prize. Carey also has played on the World Poker Tour in the Hollywood Home games for the Cleveland Public Library charity. In June 2007, Carey offered to donate up to $100,000 (in $10,000 increments) to the Mooch Myernick Memorial Fund if anybody could beat him at the video game FIFA Soccer 07 for the Xbox 360. He dared five players from both the U.S. Men's and Women's National Teams to compete against him. Carey ended up donating $100,000, plus $60,000 for losing two games out of the six games he played.

After suffering chest pains while filming The Drew Carey Show in August 2001, Carey went to the hospital, where he underwent a coronary angioplasty. Although his weight was a comedic topic throughout his sitcom and improv shows, in 2010, he began a diet and exercise plan, resulting in an extensive weight loss. He also claimed that he had cured his Type 2 diabetes as a direct result.

Carey provided the entertainment for the 2002 Annual White House correspondents' dinner. Once Carey completed his stand-up routine for the 1,800 guests, President George W. Bush, noting Carey's improv work, made a joke of his own: "Drew? Got any interest in the Middle East?" In 2003, he joined Jamie Kennedy to host the WB's live special Play for a Billion. In September 2003, Carey led a group of comedians, including Blake Clark and The Drew Carey Show's Kathy Kinney, on a comedy tour of Iraq.

Carey competed against five other celebrities in the first Celebrity edition of the 2003 World Poker Tour. He placed fifth, beating out only actor Jack Black. Carey won $2,000 for his charity.

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 canceled by the WB, but picked up shortly afterward by Comedy Central. The show's premise relied on the use of a green screen for all of the actors' improv interactions. Animation on the screen was inserted during post-production.

Carey can sometimes be seen on the sidelines of U.S. National Team soccer games as a press Photographer. His images are sold via wire services under the pseudonym Brooks Parkenridge. He was at the 2006 FIFA World Cup in the summer of 2006, for his television show Drew Carey's Sporting Adventures.

Carey has spoken about his various political beliefs in several interviews, and in 1998, he led a "smoke-in" in defiance of California's newly passed no-smoking ordinance inside bars and restaurants. Carey has hosted a series of mini-documentaries called The Drew Carey Project on Reason.tv, an online project of Reason Foundation, a libertarian-oriented nonprofit think tank (for which Carey sits as a member of the board of trustees). The first episode, "Gridlock", addresses private highway ownership and was released on October 15, 2007. Other episodes discuss topics such as eminent domain, urban traffic congestion, and medical marijuana.

In October 2009, Carey made a bid of $25,000 in a charity auction for the @drew Twitter account. He later increased his offer to $100,000 if the number of followers of his account @DrewFromTV reached 100,000 by the end of the auction. In an interview with CBS News, he said he would instead donate $1 million to the charity Livestrong Foundation if his follower count reached one million by December 31, 2009.

On May 15, 2011, Carey completed the "Marine Corps Historic Half Marathon" in 1:57:02; then, on September 4, 2011, he improved to complete the Disneyland Half Marathon in 1:50:46. And on October 30, 2011, he finished the Marine Corps Marathon with a chip time of 4:37:11, placing 10,149th out of 20,940.

Another of Carey's offers to contribute in helping others came in September 2014 when he promised $10,000 to help find the perpetrators of a faked "ice bucket challenge" involving an autistic 14-year-old Ohio boy who, instead of being doused in ice cubes and water, received a shower of feces, urine, spit and cigarette butts. Shortly thereafter, celebrities Donnie Wahlberg, Jenny McCarthy and Montel Williams matched Carey's offer.

On March 6, 2018, Carey appeared in an episode of NCIS as an ex-marine.