The Baltimore Orioles took Darnell McDonald with the 26th overall pick in 1997, but he never really found his footing in the Majors until 2009 at age 30 with Cincinnati. This long path included a four game cup of coffee with the Twins in 2007.

He did debut with the Orioles in 2004, but played just 17 games for them. McDonald spent time in the Guardians, Devil Rays, and Nationals systems on minor league deals after being released by Baltimore. Washington traded him to the Twins in June 2007 for the right to keep Rule-5 Draft pick Levale Speigner after taking him off the 25-man roster. McDonald went 1-for-10 with a walk in four appearances with Minnesota over four games in July 2007. He became a free agent after the season.

2008 was another year of exclusive minor league action for McDonald, but he got his first extended Major League look with the Reds in 2009. McDonald appeared in 47 games for Cincinnati, batting .267 and hitting his first big league homer off a 21-year old Clayton Kershaw.

This was followed up by a career year with the Red Sox in 2010. McDonald played in 117 games for Boston that season, getting to start in centerfield for an extended period of time after Jacoby Ellsbury was injured. He stuck around with the Red Sox as a fourth outfielder until getting waived in July 2012. McDonald had brief stints with the Yankees and Cubs, retiring after the 2013 season.

McDonald coached in the Cubs minor league system for a little bit, but he has since moved to broadcasting. NESN, the Red Sox television partner, hired him as a studio analyst ahead of the 2023 season.