He played in Major League Baseball (MLB) for the San Diego Padres, Tampa Bay Rays, and Colorado Rockies.

He was tied for first in the league in starts and shutouts with one, ranked second in innings pitched, third in wins and eighth in ERA.

Ekstrom was named the Padres' 2006 Minor League Pitcher of the Year after posting a 10–11 record with four complete games, two shutouts and a 3.08 ERA in 28 starts between Class-A Advanced Lake Elsinore Storm and the Double-A Mobile BayBears.

In the 2008 season, Ekstrom went 0–2 with a 7.45 ERA, six strikeouts and seven walks and held opponents to a .222 average in four road games with the Padres.

He made his MLB debut on September 10, 2008, striking out Manny Ramirez and pitching two scoreless innings.

He ranked second in the Texas League in wins and was 7–3 with a save and a 2.57 ERA (in 26 relief appearances with San Antonio.

On October 29, 2012, Ekstrom signed a minor league deal with the Athletics that included an invitation to spring training.