Crisp was born in Los Angeles on November 1, 1979. He is the son of Loyce Crisp, a fast food restaurant owner and former amateur boxer, and Pamela Crisp, a former champion sprinter. He is a graduate of Major League Baseball’s Reviving Baseball in Inner Cities Program. His maternal grandfather is Nick Newton, a masters world record holder from 1994-1996 and inventor of cast aluminum starting blocks. He played on the 1995 Senior Division RBI World Series champions from Los Angeles.

The St. Louis Cardinals selected Crisp in the seventh round of the 1999 MLB Draft. In his minor league career, Crisp played for Cardinals affiliates in four different leagues from 1999 to 2001 and was the Cardinals 2001 Minor League Player of the Year. He opened the 2002 season with the New Haven Ravens, then the Double-A Eastern League affiliate of the Cardinals. He was traded to the Cleveland Indians on August 7, 2002, to complete an earlier trade for pitcher Chuck Finley. In the Indians organization, he played for their Double-A affiliate, the Akron Aeros, and their Triple-A affiliate, the Buffalo Bisons. Crisp had 69 hits, one home run, and 24 RBI before being called up by the Indians. Crisp never had any major league experience with the Cardinals.

Crisp became the starting center fielder with the Indians in mid-2002, replacing the injured Matt Lawton. For the next few seasons, Crisp established a reputation as an excellent fielder and speedy baserunner. Despite his success, Crisp had to fight for his roster spot each spring. In 2005, Crisp moved to left field following the emergence of another young outfielder, Grady Sizemore. In his final two seasons with the Indians, Crisp showcased his offensive talent by batting .297 and .300 with 31 total home runs and 35 steals.

After Johnny Damon signed with the New York Yankees, the Red Sox sought Crisp to fill Damon’s role as both leadoff hitter and in center field. In January 2006, the Red Sox sent prospect third baseman Andy Marte, pitcher Guillermo Mota, catcher Kelly Shoppach, a player to be named later (Minor Leaguer Randy Newsom), and cash considerations to the Indians for Crisp, catcher Josh Bard and pitcher David Riske.

Crisp began the 2007 season struggling offensively due to lingering effects of off season surgery to his left index finger . On April 20, 2007, Crisp fell over a short wall at Fenway Park while trying to catch a home run by Alex Rodriguez. Although he was unable to make the catch, missing by inches, he hit a game-tying triple off Mariano Rivera in the bottom of the eighth, then scored the go-ahead run on Alex Cora’s soft line drive single. The Red Sox went on to win 7–6. During this season, he made numerous impressive catches in the outfield. It has even been claimed by one major league club that Crisp is easily the best defensive center fielder in all of Major League Baseball. Although he struggled at the plate throughout much of the season, between June 13 and July 23, Crisp raised his batting average from .221 to .284, a .402 average during that span. On June 18, entering the game with only two home runs in the season, Crisp belted two homers in the first multi-HR game of his career in a 9–4 loss to the Atlanta Braves.

On November 19, 2008, Crisp was traded to the Kansas City Royals for relief pitcher Ramón Ramírez.

During his lone season with the Royals, Crisp started off hot, hitting well over .300 before his batting average fell to a career low .228 due to shoulder injuries. On June 23, 2009, Royals manager Trey Hillman announced that Crisp would receive season ending surgeries to repair a labrum tear in both shoulders.

After the 2009 season, Crisp signed a one-year contract with the Oakland Athletics worth $5 million, with a club option for 2011. Crisp began the 2010 season on the 15-day DL with a fractured left pinkie finger.

Crisp re-signed with Athletics on January 3, 2012, on a two-year, $14 million deal with a club option for 2014. Crisp had received other offers from clubs such as the Baltimore Orioles and Chicago White Sox as well, but declined them both.

On October 10, 2012, in Game 4 of the 2012 American League Division Series against the Detroit Tigers, Crisp came to bat in the bottom of the ninth inning. The score was tied 3–3, there were 2 outs and a runner on second base (Seth Smith). The A’s were down 3–1 entering the inning, but subsequently tied the game with three straight hits off Detroit pitcher José Valverde, thus setting the stage for Crisp. He came through with a walk-off single to right field that scored Smith, giving the A’s a 4–3 win and forcing a decisive Game 5. On October 11, 2012 the Tigers finished off the series with a 6–0 victory over the A’s.

Crisp was originally nicknamed “Coco” by his sister who teased him that he looked like one of the characters on the Cocoa Krispies cereal box. The nickname was short-lived, until he started playing AA baseball when the team had all the players fill out a questionnaire to get to know one another. Covelli listed “Coco” as his nickname on the form and his teammates thought the name was funny so they had it put on the scoreboard during the game. He was traded to another team after a week and a half, but the nickname stuck and he has been “Coco Crisp” ever since. He officially changed his name on March 5, 2013.

After the 2013 season, the Athletics exercised their club option on Crisp for the 2014 season. Before the 2014 season, Crisp signed an extension with the Athletics covering the 2015 and 2016 seasons. The contract guaranteed him $11 million in each of the 2015 and 2016 seasons, and had a vesting option for the 2017 season. Crisp’s playing time was reduced in 2016, leading him to believe that the Athletics were intentionally preventing his 2017 option from vesting.

In 2015, he batted a career-low .175 and had the lowest on-base percentage (.252) and slugging percentage (.222) of his career, as on defense he played exclusively in left field.

On August 31, 2016, the Athletics traded Crisp with cash considerations to the Indians for Colt Hynes. Before he agreed to waive his no-trade clause, Chris Antonetti, the Indians’ general manager, spoke with Crisp to tell him that he would not receive enough playing time in Cleveland for his option to vest. In 2016, he batted .208 for Cleveland.

On October 10, 2016, against the Boston Red Sox in Game 3 of the ALDS, Crisp hit a go-ahead two-run home run, which would eventually be the game-winner after the Indians won 4-3. The Indians’ win propelled them to the ALCS against the Toronto Blue Jays. It was Crisp’s second career postseason home run. However, he and the Cleveland Indians could not hold on in the World Series, losing the Series in Game 7 to the Chicago Cubs.

Crisp became a free agent following the 2016 season after he failed to meet the contractual incentives that would have caused his vesting option for 2017 to trigger. In July 2017, Crisp became the head coach of the Shadow Hills High School baseball team. He has since resigned as head coach due to him and his family moving.

In February 2019, it was announced that Crisp would be joining the Oakland Athletics Radio Network as a part-time color analyst, working alongside Ken Korach and Vince Cotroneo in the booth for 33 games in the 2019 season.