Kendrick attended West Nassau High School in Callahan. He was an undersized high schooler at 5 feet 7 inches (1.70 m) and 110 pounds (50 kg) and did not have the benefit of being able to play travel ball. He played before recruiters from several colleges but received no interest until he enrolled at St. Johns River Community College in Palatka, Florida, where he was named Conference Player of the Year. It was by chance that Angels scout Tom Kotchman discovered him there in 2002. “My goodness, the kid hit the ball,” he recalled. “I couldn’t believe there weren’t other scouts there. And other JCs cut this guy? What were they thinking?”

The Los Angeles Angels of Anaheim selected Kendrick in the tenth round of the 2002 Major League Baseball draft. Baseball America named him the best prospect in the Texas League in 2005, calling him “the clear standout” in a league that also featured Kendrys Morales, Erick Aybar, and Andre Ethier. He was named the 12th top prospect by Baseball America in 2006.

Kendrick made his MLB debut on April 26, 2006, as the starting second baseman for the Angels against the Detroit Tigers. He was hitless in four at-bats in the game. His first hit was a line drive single to center off Barry Zito of the Oakland Athletics in his next start, on May 1. Kendrick hit his first home run against Shawn Camp of the Tampa Bay Devil Rays on July 26. He hit .285 with 4 homers and 30 RBIs in 72 games during that season.

Kendrick and his wife Jody married on January 6, 2007. They have two sons, Owen and Tyson. Kendrick is a vintage watch collector. Kendrick is an avid photographer known for shooting exclusively with Leica cameras.

After the incumbent starter, Adam Kennedy, signed as a free agent with the St. Louis Cardinals during the 2006-2007 offseason, Kendrick became the Angels starting second baseman for 2007. He batted .322 in 88 games and again batted over .300 in 2008.

Kendrick extended his positional versatility in the 2011 season, seeing time at first base and left field in addition to his usual place at second base. In 2011, Kendrick was selected to serve as an American League reserve in the 2011 All-Star Game. He joined teammates Jered Weaver, and Jordan Walden as the Angels’ representatives in Phoenix, Arizona. Through the All-Star break on July 10, Kendrick was hitting .302/.360/.462 with 8 home runs, 9 stolen bases, and 29 RBIs in 301 at-bats.

On January 7, 2012, Kendrick agreed to a new four-year contract worth $33.5 million, making him the Angels’ second baseman through the 2015 season. Kendrick had a strong 2012 season, batting .287 with 8 home runs and 67 RBIs.

On July 30, 2013, Kendrick got his 1,000th career hit in a game versus the Texas Rangers. Kendrick would improve on his 2012 campaign with an even stronger 2013, batting .297 with 13 home runs and 57 RBIs. In 2014, he hit .292 with 7 homers and 75 RBIs.

On December 10, 2014, the Angels traded Kendrick to the Los Angeles Dodgers in exchange for Andrew Heaney. Kendrick suffered a strained hamstring in a game on August 9 and did not return from the disabled list until September 18, though the injury would continue to bother him for the rest of the season. As a result, he played in only 117 games for the Dodgers (his lowest total since 2009) and hit .295 with 9 homers and 54 RBI. He received a qualifying offer for one year of $15.8 million, but declined it.

On February 4, 2016, Kendrick re-signed with the Dodgers on a two-year, $20 million contract. Kendrick and his agent blamed the fact that he declined the qualifying offer and thus would require any team claiming him to give up a draft pick with the lack of interest in him from other teams during his free agency. With Chase Utley getting most of the work at second base, Kendrick played primarily in left field but also saw time at third base and first base in addition to second. He appeared in 146 games and hit .255/.326/.366 with eight homers and 40 RBI. For the season, he had the highest ground ball percentage (61.0%), and the lowest fly ball percentage (19.6%), of all major league hitters.

Kendrick was traded to the Philadelphia Phillies for Darin Ruf and Darnell Sweeney on November 11, 2016.

On April 18, 2017, Kendrick was placed on the 10-day disabled list due to a strained right abdomen.

On July 28, 2017, the Phillies traded Kendrick and cash considerations to the Washington Nationals for McKenzie Mills and international signing bonus money. On August 13, Kendrick hit his first grand slam, a walk-off in the bottom of the 11th, against the San Francisco Giants. He batted .293 that season, finishing with 7 HR and 25 RBI. He primarily played left field.

He re-signed with the Nationals after the season for two years and $7 million plus incentives. On May 19, 2018, Kendrick ruptured his Achilles, ending his season early. He finished the season batting .303 with 4 HR and 12 RBIs.

Kendrick participated in 121 regular season games in 2019, finishing with a batting average of .344 in 330 at bats, alongside 62 RBIs and 17 home runs, second-most of any season in his career. He primarily played first base.

On October 9, 2019, in Game 5 of the National League Division Series, Kendrick hit a grand slam in the 10th inning off Los Angeles Dodgers pitcher Joe Kelly to give the Nationals a 7-3 lead that held up as the final score, advancing the Nationals to the National League Championship Series. It was just the second extra-innings grand slam in MLB postseason history, the other being hit by Nelson Cruz in the 2011 American League Championship Series.

Kendrick became a free agent after the 2019 season, but on December 9, 2019, Nationals general manager Mike Rizzo said he had signed a new deal to stay with the Nationals. The contract reportedly covers the 2020 season and will pay Kendrick $6.25 million.