Penny played in Major League Baseball (MLB) for the Florida / Miami Marlins, Los Angeles Dodgers, Boston Red Sox, San Francisco Giants, St. Louis Cardinals, and Detroit Tigers, and in Nippon Professional Baseball (NPB) for the Fukuoka SoftBank Hawks.

[1] He graduated from Broken Arrow Senior High where he was an All-State selection and Frontier Conference Pitcher of the Year.

Penny combined with Luis Arroyo for the first no-hitter in Portland history in his first game in the Marlins' organization on August 8.

Penny collected the win in Florida's NLCS clinching victory over the Chicago Cubs and in the World Series against the New York Yankees he went 2–0 with a 2.19 ERA in his two starts.

On July 30, 2004, Penny was traded along with Hee-Seop Choi and pitching prospect Bill Murphy to the Los Angeles Dodgers in exchange for Guillermo Mota, Juan Encarnación, and Paul Lo Duca.

On June 12, 2005, Penny signed a three-year contract extension worth a guaranteed $25 million and a team option for the 2009 season.

[6] On September 23, 2006, against the Arizona Diamondbacks, Penny joined the small club of pitchers who have struck out four batters in one inning.

For the 2008 season, Penny was selected as opening day starter against the San Francisco Giants, shutting them out over seven innings, but he struggled in 2008 overall, going 6–9 with a 6.27 ERA and a stint on the DL.

[8][9][10] Penny recorded his 100th career win on June 17, 2009, against his former team the Florida Marlins, in a five inning effort only giving up one unearned run.

After a disastrous start against the rival Yankees, it was decided on August 22, 2009, that Penny would be replaced in the rotation by veteran knuckleballer Tim Wakefield who was coming off the disabled list soon.

[14] On May 21, 2010, Penny hit his first career grand slam, to give his team an 8–4 lead during interleague play against the Angels.

The injury was an aggravation of a pre-existing oblique muscle strain that landed him on the disabled list for the remainder of the season.

He became a free agent following the season On January 18, 2011, Penny agreed to a one-year $3 million contract with the Detroit Tigers.

[15] Being added to the Tigers roster reunited Penny with past teammates in Miguel Cabrera from the Marlins and Victor Martinez from the Red Sox.

Penny started off the season with the Tigers as their number two starter, behind Justin Verlander and in front of Max Scherzer.

On February 5, 2012, Penny agreed to a one-year $3 million contract with the Fukuoka SoftBank Hawks of Nippon Professional Baseball.

[19] He was a "huge disappointment,[20]" and a local newspaper reported that signing Penny was "the worst decision in franchise history.

[26] He had his contract selected to the major league roster and he made his first start with the club on August 9, 2014, against the Cincinnati Reds.

[27] After a mixed spring training in 2015 (1-1 record with a 6.89 ERA in 15.2 innings),[28] he failed to win a spot in Chicago's rotation and played with their Triple-A affiliate, the Charlotte Knights, in the International League.

[29] On December 18, 2015, Penny signed a minor league contract with the Toronto Blue Jays that included an invitation to spring training.