He first pitched in a professional league for the Class A Auburn Doubledays in 2007. In 2008, he was promoted to the Dunedin Blue Jays, and later to the Double-A New Hampshire Fisher Cats, and finally to the Triple-A Syracuse Chiefs. He received an invitation to attend spring training with the Blue Jays in 2009, but began the season in Triple-A.
Cecil was called up to the Toronto Blue Jays on May 1, 2009, and made his major league debut on May 5 as the starting pitcher against the Cleveland Indians at home. In that game, Cecil pitched six innings, giving up two runs, one earned, and six hits but was credited with a no-decision in a game Toronto eventually won. His next start was May 10 against the Oakland Athletics, pitching 8 scoreless innings to earn his first Major League win. Cecil defeated the Chicago White Sox, keeping Toronto in first place, but then gave up five home runs to the Boston Red Sox on May 21, losing his first game, as Toronto went on a nine-game losing streak and dropped out of first place. Cecil was returned to AAA after losing to Boston, and then pitched solidly for the Las Vegas 51s. Continued injury problems for Blue Jays' pitchers led to Cecil being recalled to the major leagues on June 18, and he started against the Washington Nationals on June 20, filling in for the injured Casey Janssen and Roy Halladay, pitching 7 innings while allowing 3 earned runs in a no-decision, in a game Toronto lost in 12 innings.
Originally not making the rotation for the Blue Jays, Cecil was called up early in the season and became a regular in the Jays rotation along with Ricky Romero, Shaun Marcum and Brandon Morrow. On May 3, 2010, he took a perfect game into the seventh inning against the Cleveland Indians, but walked Grady Sizemore with one out. Then, two batters later, he allowed a single to Jhonny Peralta which scored Sizemore from second to end his no-hitter and his shutout. He ended up going 8 innings, allowing one hit, 2 walks, one run, and 10 strikeouts. Despite not making the original team out of spring training he led the team in wins with 15, along with a much improved 4.22 ERA.
To start the 2011 season, Cecil went 1–2 with a 6.86 ERA, which led to the Blue Jays optioning him to Triple-A, in order to make room for Chris Woodward on the 25-man roster. He was later recalled in late June and lost in his first start, against the Pittsburgh Pirates. On July 24, he pitched his first complete game shutout against Texas Rangers. Cecil finished the 2011 season with a 4–11 record and an ERA of 4.73.
Cecil started the 2013 season in the Blue Jays bullpen. On June 19, against the Colorado Rockies, Cecil broke the club record for facing the most consecutive batters without allowing a hit, set by David Cone with 36. Cecil's hitless streak ended after 43 consecutive batters on June 25, against former teammate Yunel Escobar and the Tampa Bay Rays. On July 6, Cecil was named to the AL All-Star Team, which was special for Cecil considering the fact that it is rare for a mid relief pitcher to earn an All-Star appearance. Cecil pitched ⁄3 of an inning in the All-Star Game, striking out Domonic Brown on 3 pitches. On July 31, Cecil recorded his first career save in a 5–2 win over the Oakland Athletics. He was placed on the disabled list on September 17, ending his 2013 campaign with a 5–1 record, 2.82 earned run average, and 70 strikeouts over 60⁄3 innings.
In January 2014, Cecil filed for salary arbitration with Toronto, but came to terms on a 1-year, $1.3 million contract on January 17. He pitched the entire season out of the bullpen, making a career-high 66 appearances. In 53⁄3 innings pitched, Cecil posted a 2–3 record with a 2.70 ERA and 76 strikeouts. He also recorded 5 saves, and gave up only 2 home runs for the entire season.
On January 15, Cecil signed a one-year, $2.475 million contract with Toronto to avoid salary arbitration. With the departure of Casey Janssen in the offseason, the role of closer was left vacant into spring training. On March 24, manager John Gibbons named Cecil the Blue Jays' closer to open the 2015 season. Cecil struggled to open the 2015 season, and lost the closer role early to rookie Miguel Castro. On April 28, Cecil was moved back into the closer role. After yielding 8 earned runs in his previous 2⁄3 innings pitched, Cecil was again removed from the closer role on June 23. From June 24 through the end of the season, Cecil did not allow an earned run, lowering his ERA from 5.96 to 2.48. He was named to the postseason roster and appeared in both of the Blue Jays first two games, however he suffered a calf injury in the second game. Afterward it was determined that he would miss the remainder of the postseason with a tear in his left calf muscle.
Cecil signed a four-year, $30.5 million contract with the St. Louis Cardinals on November 21, 2016. In 2017 he was 2-4 with a 3.88 ERA.
