Between 2007 and 2023, he played 17 seasons in Major League Baseball (MLB) for the New York Yankees, Arizona Diamondbacks, San Diego Padres, Kansas City Royals, Texas Rangers, and Philadelphia Phillies.

A standout pitcher at La Quinta High School in California, Kennedy played three seasons of college baseball for the USC Trojans.

The Royals moved Kennedy to the bullpen in 2019 after a series of injuries, and he found a new role as the team's closer, and he continued to work as a relief pitcher for the remainder of his career.

[2] Kennedy began gaining a reputation as a power pitcher when he was a freshman at La Quinta High School in Westminster, California, pitching a five-inning perfect game.

Kennedy was tapped as the starting pitcher for the US team's bronze medal match at the 2002 World Junior Baseball Championship, where he took the win with only one earned run and 10 strikeouts in seven innings of work.

[9] USC baseball coach Mike Gillespie opened the 2005 season with the intention of using Kennedy up to three times a week, pitching on Fridays, Sundays, and Tuesdays to limit the damage of the school's dearth of starting pitchers.

[10] His sophomore year turned into a breakout season for Kennedy, who went 12–2 with a 2.54 ERA, earned consensus All-American honors, and helped lead the Trojans through the first round of the 2005 NCAA Division I baseball tournament.

[13] Going into the 2006 college baseball season, USC lost many staples of its rotation to the MLB draft, including catcher Jeff Clement and third baseman Billy Hart, and Kennedy was called upon to be a leader for the younger members of the team.

[25] He made his major league debut on September 1, 2007, allowing only one earned run in seven innings of an eventual 9–6 victory over the Tampa Bay Devil Rays.

[26] After going 1–0 with a 1.89 ERA in his first three major league starts, Kennedy had to be scratched from a scheduled September 22 game against the Toronto Blue Jays because he strained a muscle in his upper back.

[28] The plan did not work as expected: Kennedy went 0–2 with an 8.37 ERA in his first six games and was optioned to Triple-A on May 4, with Darrell Rasner taking his place at the back of the rotation.

[34] Kennedy made his first Yankees appearance in over a year on September 23, walking two batters and hitting another with a pitch during the eighth inning of an eventual 3–2 win over the Angels.

[39] The Diamondbacks' player development staff agreed at the start of the season to limit Kennedy's workload to a total of 180 innings, an amount that would help the pitcher extend his durability without pushing him into additional injuries.

[43] Arizona manager Kirk Gibson tapped Kennedy to serve as the Diamondbacks' opening day starter for the 2011 season, after he went 0–0 with a 7.88 ERA during spring training.

[45] After a brief trip to New York to be with his wife and their newborn child, Kennedy pitched his first major league complete game on April 25, outdueling ace Cliff Lee in a 4–0 shutout of the Philadelphia Phillies.

[52] Kennedy was called upon to start Game 1 of the 2011 National League Division Series against the Milwaukee Brewers, pitching opposite Yovani Gallardo.

[56] In his next start, after making a "secret" mechanical change to his pitches, Kennedy matched his career high 12 strikeouts in a 10–0 shutout of the Colorado Rockies.

In the bottom half of that inning, Kennedy struck Greinke in the helmet with a pitch, leading to a benches-clearing brawl between the Dodgers and Diamondbacks, with six players and coaches ejected from the game.

[61] Kennedy was suspended for 10 games for what MLB referred to as "intentionally throwing a pitch in the head area of Zack Greinke ... after a warning had already been issued to both clubs".

[65] The Padres immediately added Kennedy to their starting rotation, where he joined Andrew Cashner, Tyson Ross, Eric Stults, and Edinson Volquez.

[43] Going into the 2014 season, Padres manager Bud Black placed Kennedy in the second spot of the starting rotation, between opening day starter Andrew Cashner and No.

He recovered through the middle part of the season, striking out 93 batters in 16 starts between June and August while holding his opponents to a .229 batting average, but struggled again at the end of the year.

[76] On January 16, 2016, the Kansas City Royals signed Kennedy to a five-year, $70 million contract, with an opt-out clause built in prior to the 2018 season.

[82] While Kennedy was mostly happy with his performance during the 2016 season, in which he went 11–11 with a 3.68 ERA and struck out 184 batters in 195+2⁄3 innings, he was disappointed that the Royals did not reach the postseason, and his 33 home runs allowed were "a lot more" than he had been "expecting or hoping for".

[89] Most of Kennedy's summer was taken up with a left oblique strain: he was originally put on the 10-day disabled list for the injury at the end of June, with a return date of July 10.

[92] Kennedy himself was hesitant to make the change, believing that he was capable of another year in the starting rotation, but he ultimately had a successful stint as the Royals' closer.

[94] For the period between May 30 and September 23, Kennedy led MLB with 28 saves, including 19 after the All-Star break, and he noticed a physical improvement to becoming a reliever, in contrast to feeling "like you get hit by a truck every fifth day" as a starting pitcher.

[43] Upon learning that the 2020 MLB season would be shortened to 60 regular-season games as a result of the COVID-19 pandemic, Royals manager Mike Matheny decided not to assign any permanent roles like closer or setup man for his bullpen.

[96] At the end of the month, he was placed on the injured list when he suffered a left calf strain in the ninth inning of a game against the Chicago White Sox.

[127] Kennedy was a recipient of the 2019 Bob Feller Act of Valor Award, presented to baseball players for their continued support of members of the United States military.