Reagins resigned as the Angels have not made the playoffs for the second season in a row.
Reagins took over for Bill Stoneman after the 2007 season. In his first two seasons as general manager, the Angels won the American League West Division.
Despite starting this season with baseball's fourth-highest payroll at $139 million, Los Angeles went 86-76 and finished 10 games behind Texas in the AL West and five behind Tampa Bay in the wild-card race.
The Angels said Reagins will remain with the team as a special assistant to chairman Dennis Kuhl.
Before he became the Angels GM, Reagins spent the previous six seasons as Los Angeles' director of player development under Stoneman, his mentor. Los Angeles won a majors-best 100 games in his first season in 2008 before getting within two games of the World Series in 2009.
Reagins started with the Angels as an intern in 1991.
The Associated Press contributed to this report.