He played in Major League Baseball (MLB) for the New York Yankees, Pittsburgh Pirates, San Diego Padres, Washington Nationals, Texas Rangers, and Cincinnati Reds, and in the Nippon Professional Baseball (NPB) for the Tokyo Yakult Swallows.

[1] He graduated from St. Stephen's Episcopal High School in Austin in 2001 where he was a two-sport athlete, playing basketball and baseball.

[5][6] As a student, he penned a 140-page senior thesis entitled Investing in Prospects: A Look at the Financial Successes of Major League Baseball Rule IV Drafts from 1989 to 1993.

[8] He received the George Mueller Award from the university for combining "high scholarly achievement in the study of engineering with quality performance in intercollegiate athletics".

In his senior thesis, Ohlendorf used sabermetrics to demonstrate the return on investment from the Major League Baseball Draft.

In 2006, playing for the Diamondbacks AA affiliate, the Tennessee Smokies, Ohlendorf went 10–8 with a 3.29 ERA and led the Southern League with four complete games, earning a promotion to AAA Tucson for one playoff start.

Before the 2007 season, the Diamondbacks traded Ohlendorf, Luis Viscaino, Alberto Gonzalez, and Steven Jackson to the New York Yankees for Randy Johnson.

[11][12][13] Yankees General Manager Brian Cashman said of Ohlendorf: "He's big, physical, eats innings and he's competitive.

[17] On September 15, he pitched 11⁄3 innings against the Boston Red Sox, allowing a walk and a home run, but recording all four outs on strikeouts.

[18] Ohlendorf impressed the Yankees enough in September to earn a spot on the ALDS roster, but struggled in his lone appearance in the series, allowing three runs on four hits and one walk in one inning.

[19] On July 26, 2008, Ohlendorf was acquired by the Pittsburgh Pirates from the New York Yankees in a deal with José Tábata, Jeff Karstens, and Daniel McCutchen for Xavier Nady and Dámaso Marte.

[20] Ohlendorf spent the first month pitching for the AAA Indianapolis Indians and was called up to Pittsburgh on September 2 when the rosters expanded.

[21] He was added to the starting rotation and made his first appearance on September 3 against the Cincinnati Reds where he pitched six innings and allowed four runs (three earned) in a 6–5 Pirates victory.

Pirates General Manager Neal Huntington would say, "We're looking forward to working with him to put him in position to where he can be a 200-plus inning starter for many, many years to come.

Ohlendorf was hit in the head by a line drive off of Troy Tulowitzki's bat in a July 28, 2010, game against the Colorado Rockies.

[31] On September 15, Ohlendorf hit his first career home run off Dana Eveland, also becoming the first Pirates pitcher to homer since Paul Maholm did so on May 9, 2009, against the New York Mets.

[37] Ohlendorf made nine starts in 13 total appearances for the Padres and posted a 4–4 record and a 7.58 ERA in 482⁄3 innings.

[47] In the 14th inning of Game 2 of the 2015 American League Division Series, Ohlendorf would pick up a save in the Rangers 6-4 win over the Toronto Blue Jays.