Wakamatsu, who took over in November 2008, had an 85-77 record last year and went 42-70 this season as the Mariners slumped to last place in the American League West Division.
"I have concluded these changes needed to be made now and they are in the best interest of the Mariners as we move forward," Seattle's general manager of baseball operations Jack Zduriencik said in a statement.
Expectations were heightened in the off-season when the team acquired left-handed pitcher Cliff Lee, who has since been traded, in a bid to boost their rotation.
The Mariners also dismissed three coaches on Monday and named Daren Brown, manager of Seattle's Triple-A affiliate, the team's interim manager for the rest of the season.
(Writing by Frank Pingue in Toronto, editing by Tony Jimenez)