He played in Major League Baseball (MLB) for the Atlanta Braves, Kansas City Royals and Arizona Diamondbacks.

As of 2023, Medlen works for Bally Sports South where he serves as an on-air analyst for Atlanta Braves baseball telecasts.

[4] Medlen played his first professional baseball game on June 22, 2006, for the Danville Braves of the Appalachian League.

He appeared in 20 games for Danville, and pitched a total of 22 innings, being credited with 1 win, no losses, and 10 saves.

[5] His statistics for these three teams were as follows: For the Rome Braves, Medlen appeared in 17 games, logging 20.2 innings, with 33 strike-outs and 3 walks; he had an ERA of 0.87 and a WHIP of 0.774.

For the Myrtle Beach Braves, Medlen appeared in 18 games, pitching 24 innings, with 28 strike-outs and 9 walks (2 of them intentional); he had an ERA of 1.12 and a WHIP of 1.230.

[8] Medlen began his major league career as a starter, making his debut on May 21, 2009, pitching just 3.0 innings, giving up 5 earned runs on 3 hits against the Colorado Rockies.

[12] On August 5, 2010, Medlen was placed on the 15-day disabled list with a partially torn ulnar collateral ligament tear in his right elbow.

It was announced by the Atlanta Braves that he would require Tommy John surgery to repair the damage, ending his season.

Medlen got his first start of the 2012 season, on July 31, 2012, against the Miami Marlins, allowing 4 hits and 1 earned run and recording the win in a 7–1 game.

On August 11, 2012, in a 9–3 win against the Mets at Citi Field, Medlen pitched 6.1 innings, allowing 5 hits and 1 walk, while striking out 7.

[17] Perhaps the most important win of Medlen's professional career came on August 22, at Washington, with the Braves ending a four-game losing streak that had included two games against the Division-leading Nationals.

On September 3, 2012, Medlen faced the Colorado Rockies at Turner Field, and got the win in dominant fashion.

Medlen pitched a complete game, allowing five hits and no walks while striking out a career-best 12 batters.

[22] On September 8, 2012, Medlen faced the New York Mets at Citi Field, and recorded his 8th win of the season.

[24] On September 14, 2012, Medlen got the start against the first-place Washington Nationals, at Turner Field, and pitched 7.0 innings, leaving with the score tied at 1–1.

In the 1st and 5th innings, Marlin runners reached third base with only one out, but a strike-out followed by a ground-out and a pop-out followed by a grounder preserved the scoreless game for Medlen.

[28] On September 30, 2012, Medlen led the Braves to their 23rd consecutive victory in games that he started, as they beat the Mets, 6–2.

In an article discussing the award, Atlanta Journal-Constitution writer David O'Brien pointed out that many commentators have been comparing Kris Medlen to the Braves' legendary pitcher, Greg Maddux.

[34] On December 18, 2014, he signed a two-year deal (with a mutual option for a third year) with the Kansas City Royals for a guaranteed $8.5 million.

[35] He started the 2015 season on the 60-day disabled list to continue recovering from his second Tommy John surgery and made his first appearance for the Royals on July 20, 2015, against the Pirates.

He was also part of the Royals postseason run as the team won the 2015 World Series over the New York Mets, their first championship in 30 years.

[44] Medlen met his wife Nicki through former minor league teammate Ryne Reynoso, and married her in 2012.