After being promoted to Single-A Cedar Rapids in 2002, he missed the entire 2003 season due to an injury in his left shoulder.

In 2005, he was a combined 10–7 with three complete games, including two shutouts, earning honors as the Angels Organization's Pitcher of the Year.

[4] Saunders made his major league debut on August 16, 2005, against the Toronto Blue Jays, receiving a no decision after closer Francisco Rodríguez blew the save in a 4–3 loss for the Angels.

After Bartolo Colón was placed on the disabled list during the 2006 season, Saunders was recalled a final time and replaced Colon in the rotation.

He also wore the initials "VT" on his cleats and drew the Virginia Tech logo on the back of the pitcher's mound before the start of the game.

In 2008, Saunders entered spring training in a competition with Santana for the role of 5th starter in the Angels rotation.

After the Angels' co-aces John Lackey and Kelvim Escobar sustained injuries, both Saunders and Santana were promoted to full-time roles as the 3rd and 4th starter, respectively.

In the first third of the season, both players shone brightly, with both being considered early candidates for the American League Cy Young Award.

On June 3, 2008, Saunders became the American League's first 9-game winner in a 5–4 victory over division rivals the Seattle Mariners.

Saunders also then became the first American League pitcher to get 11 wins, giving up only two earned runs to the Philadelphia Phillies on June 21, 2008.

Saunders was the winning pitcher when the Orioles defeated the Texas Rangers in the inaugural Wild Card Game, pitching 5+2⁄3 innings with four strikeouts.

[10] Over his first six weeks of the season, he pitched very well at home in Safeco Field and extremely poorly in his road outings.

On August 5, 2014, Saunders returned to the Baltimore Orioles, signing a minor league contract with the club.

[18] Saunders is married to his Virginia Tech classmate and former Hokie softball player, the former Shanel Garofalo.