McDonald attended Long Beach Poly High School,[1][2] where he played baseball, basketball and football.

He made the switch to outfield, thinking he could still work with trainers while keeping occupied in left field, but after sub-.230 batting averages in '04 with the Gulf Coast Dodgers and again in 2005 with the Ogden Raptors, he expressed his desire to return to pitching.

In 2006, he was back on the hill full-time for the South Atlantic League's Columbus Catfish where he led the pitching staff with an ERA of 3.97 and 147 strikeouts in 143 innings of work but only managed to finish with a record of 5–10.

He made his major league debut on September 17, 2008, against the Pittsburgh Pirates, working one scoreless inning in relief.

He made three more starts, only lasting as many as five innings in one (April 25 against the Colorado Rockies, his first career victory), and then was demoted back to the bullpen.

On July 31, 2010, McDonald was traded along with outfielder Andrew Lambo to the Pittsburgh Pirates for reliever Octavio Dotel.

[8] His performances prompted Jack Moore of Fangraphs to call McDonald an "ace" for the Pirates and the biggest steal of the 2010 MLB Trading Deadline.

Following the Atlanta game where McDonald out-dueled Braves ace Tim Hudson and struck out nine while walking none, he spoke about his control during the first half of the season.

To begin the 2012 campaign, McDonald delivered several quality starts before earning his first victory of the season on April 30 against Atlanta, a 7+2⁄3-inning, 10 strikeout performance.

On May 17, McDonald set a new career-high for strikeouts with 11 against the Washington Nationals, while also taking a no-hit bid into the sixth inning.

In 2017, McDonald became a coach for the Southwest Nationals Baseball Organization, founded by former MLB pitcher Scott Elbert.

[14] In the early part of the 2012 season, his slider was recognized as the NL's second-best swing-and-miss pitch, only behind Cole Hamels' changeup, with whiff rate of 49% since 2011.