After attending Fountain Valley High School (graduating in 1998), Wilson played at Santa Ana College where in 2000 he was named the MVP of the Orange Empire Conference, and awarded the California Junior College Co-Player of the Year award. Wilson played outfield, first base, starting pitcher, and relief pitcher at Loyola Marymount University during the 2001 season.

For 2003, Wilson returned to Double-A with Frisco RoughRiders of the Texas League, earning Pitcher of the Week honors in May. His up and down season was cut short due to injury which resulted in season-ending Tommy John surgery on August 12.

After missing all of 2004 due to the elbow injury, Wilson was able to return to Double-A in 2005 before being called up to the majors later that season. He posted a 1–7 record and 6.94 ERA in 24 games during his rookie campaign with the Rangers. Later in the season, Texas placed him in the bullpen full-time where he went 1–2 with a 2.73 ERA in 18 relief appearances.

Following the trade of Éric Gagné, Wilson was used to close out games for the Rangers in 2007 converting his first 11 consecutive chances. Overall, he finished with career bests in: ERA (3.03), appearances (66), innings (68.1), strikeouts (63), WHIP (1.21), holds (15), and opposing batting average (.208).

In 2009, Wilson returned to role of set-up man as Frank Francisco was named the closer. He set new career bests in: wins (5), innings (73.2), appearances (74), ERA (2.81), strikeouts (84), K/BB ratio (2.61), holds (19), home runs allowed (3) as well as recording 14 saves throughout the year and set a team record for the lowest home ERA for a single season (0.67).

In 2010, Wilson returned to his past role as a starting pitcher with Texas. Wilson had expressed an interest in returning to the rotation as early as 2006 and was told to report to spring training in condition to start. Early conjecture amongst sports writers and fans covering the Rangers spring training debated if Wilson would actually be able to earn a spot in the rotation. After making several impressive spring starts pitching coach Mike Maddux was asked if Wilson was making the rotation a tough call to which Maddux said, “He’s making it a great call.” Wilson was named the third starting pitcher in the rotation behind Scott Feldman and Rich Harden.

Wilson races racecars in his free time, and has mentioned he aims to be a professional racer after his baseball career; he also is highly interested in cars, having a collection of Porsches as well as a custom painted McLaren P1. Wilson won the E1 class in the 2010 25 Hours of Thunderhill. He races a Mazda MX-5 in club races and owns a race team that competes in the professional Global MX-5 Cup series.

In 2011, Wilson was 16–7 with a 2.94 ERA (seventh in the AL). He led the league in games started (34), and was fourth in wins, fifth in win-loss percentage (.696), and sixth in strikeouts (206; sixth-most in Rangers history).

On December 8, 2011 Wilson agreed to a five-year, $77.5 million deal with the Los Angeles Angels of Anaheim. This deal came only hours after Albert Pujols signed a record breaking ten-year, $250 million deal with Anaheim. The contract became official on December 10.

On May 22, 2012, Wilson and Ernesto Frieri pitched a combined one-hit shutout against the Oakland Athletics in Oakland, a place Wilson said that he strongly disliked pitching while with the Texas Rangers. Wilson struck out seven and allowed two walks while giving up a single. He was selected to the All Star game in 2012 after going 9-5 with a 2.43 ERA for the Angels. He finished the season with a 13-10 record in 34 starts. He followed the 2012 season with another successful season, winning a career high 17 games while lowering his ERA from the prior season to 3.39.

Wilson married Brazilian model Lisalla Montenegro on December 15, 2013 in Laguna Beach, California. They have two daughters.

Despite the team making the playoffs in 2014, Wilson did not have a good season, finishing with an ERA of 4.51 and leading the majors in walks with 85. Due to his high pitch counts, Wilson averaged less than 6 innings per start. Wilson’s season was cut short in 2015, starting only 21 games before going out with an elbow injury in early August. He opted for elbow surgery.

CJ Wilson owns CJ Wilson Mazda, which operates dealerships in Countryside, Illinois, Orland Park, Illinois, Lake Villa, Illinois and Ventura, California. He also is the General Manager of Porsche Fresno and raced in the 2018 Pikes Peak International Hill Climb.