He played in Major League Baseball (MLB) for the Arizona Diamondbacks, Cincinnati Reds, and Chicago White Sox.

In 2011, Holmberg split the year between the Single-A South Bend Silver Hawks and the High-A Visalia Rawhide, accumulating a 12–9 record and 3.44 ERA in 27 starts between the two teams.

The following year, Holmberg split the season between Visalia and the Double-A Mobile BayBears, pitching to a cumulative 11–8 record and 3.32 ERA with 153 strikeouts in 173.1 innings of work.

On December 3, 2013, Holmberg was traded to the Cincinnati Reds in a three-team deal also involving the Tampa Bay Rays.

[10] Holmberg started that night's game against the Atlanta Braves, but gave up six runs in two and two-thirds innings and picked up the loss.

On December 3, 2015, Holmberg signed a minor league contract with the Atlanta Braves organization that included an invitation to spring training.

He split the season between the Double-A Birmingham Barons and the Triple-A Charlotte Knights, pitching to an 8–9 record and 3.84 ERA in 28 appearances between the two teams.

[14] He made his White Sox debut the next day against the Kansas City Royals, allowing a run in two-thirds of an inning.

[19] He spent the year with the Triple-A Albuquerque Isotopes, and posted a 7–8 record and 5.21 ERA with 65 strikeouts in 107 innings of work.

[22] Holmberg posted a 6–1 record and 2.34 ERA in 12 games with Milwaukee and won the American Association championship with the team.

On April 25, 2024, Holmberg was hired to become the pitching coach for the Kane County Cougars of the American Association of Professional Baseball.