The move came after the Reds lost the wild-card playoff in Pittsburgh 6-2 on Tuesday night, ending the season with their sixth straight loss. He had a year left on his two-year deal.
The Reds are the fourth team with an opening at manager. Davey Johnson retired after the Nationals' season, Eric Wedge left the Mariners and the Cubs fired Dale Sveum after finishing last in the NL Central.
Baker took over a rebuilding team in 2008 and led it to three 90-win seasons and playoff appearances in the last four years, their best run since Sparky Anderson managed the Big Red Machine to two World Series titles in the 1970s.
Cincinnati couldn't get past the opening round of the playoffs, however, building pressure for change.
"Dusty played an important role in the recent success of this organization, and we thank him for his contributions during his time here," general manager Walt Jocketty said in a statement. "We feel a change is necessary, however, if we are to continue to move the organization forward."
The 64-year-old manager didn't get to celebrate the Reds' last two playoff clinching wins. Last year, he was in a hospital in Chicago recovering from an irregular heartbeat and a mini-stroke when the Reds wrapped up the NL Central title in Cincinnati.
They decided not to celebrate when they clinched a wild card this year with a 90-72 record, hoping for that deep run in the playoffs. Instead, they lost their last five games of the regular season to finish third and dropped the one-game playoff at PNC Park.
Baker went 509-463 in his six seasons with Cincinnati, finishing third on the Reds' list for wins by a manager behind Anderson (863) and Bill McKechnie (744). His 1,671 career wins ran 16th on the career list. He won three NL Manager of the Year awards.
The former Braves and Dodgers star outfielder is one of only six managers to win at least 300 games with three different teams. He took the Giants, Cubs and Reds to the playoffs seven times without winning a World Series.
His closest brush came in 2002 with the Giants, who beat the Braves and the Cardinals before losing to the Angels in a seven-game World Series. He's 19-26 all-time in the postseason.
His successor in Cincinnati will take the job with enormous expectations from the outset.
Baker led the Reds out of one of their worst stretches in franchise history. After Johnson led them to the NL championship series in 1995, the bottom fell out. They failed to reach the playoffs under managers Ray Knight, Jack McKeon, Bob Boone, Dave Miley and Jerry Narron, going 15 years without a postseason appearance.
They won the division in 2010 with a young lineup that developed faster than expected, and got swept by Philadelphia in the first round of the playoffs - a disappointment that was counted as a first step in building a championship team.
They won 97 games last year, the second-most in the majors and their highest total since the 1975-76 World Series championships. They won their first two playoff games in San Francisco, but dropped three straight in Cincinnati for a stunning exit.
Baker led the Reds to 90 wins again this season - the eighth time one of his teams won 90 - but the offense went into a deep slump in the final week. The Pirates swept a three-game series in Cincinnati to end the season and clinch home-field advantage for the wild-card game, then finished them off at raucous PNC Park.
A rough ending to a tough season all-around.
The Reds reached the playoffs despite playing in the NL's toughest division and losing both of their setup relievers and their cleanup hitter to injuries for most of the season. They have two players who can leave as free agents - center fielder Shin-Soo Choo, who topped all leadoff hitters in on-base percentage, and starter Bronson Arroyo.
They have to decide what to do for a cleanup hitter. Ryan Ludwick tore cartilage in his right shoulder while sliding into third base on opening day and didn't return until mid-August. His shoulder continued to bother him, and he batted only .240 with two homers and 12 RBIs.
Jocketty inherited Baker as manager when he was hired in 2008. The two of them weren't always in accord on player decisions.