Reagins had served as the team's 10th GM since October 16, 2007, after taking over for Bill Stoneman. He guided the Angels to American League West titles in each of his first two seasons (2008-09), but the club failed to make the postseason in each of the last two years.
"Though we finished 2011 with a winning record, we remained short of our objective in winning a championship," said Angels owner Arte Moreno. "In moving forward, we felt a change was needed."
In 2008 -- Reagins' initial season as general manger -- the Angels posted the best record in baseball, at 100-62. It was the first time in history that the club reached the century mark in victories.
Reagins has spent his last 20 years with the Angels organization. He will remain with the club as a special assistant. No replacement has been announced.
"Throughout his career, Tony has meant a great deal to this organization, and represented the Angels with the utmost loyalty and dedication. He will always remain part of the Angels family," added Moreno.