The team announced Thursday that Price will be replaced on an interim basis by bench coach Jim Riggleman on the heels of a 3-15 start.
The Reds added that they will conduct a "thorough managerial search" later in the year to find a permanent manager.
Cincinnati, which owns the worst record in Major League Baseball, also fired pitching coach Mack Jenkins. Danny Darwin will replace Jenkins in that role, while Pat Kelly will be elevated from Louisville (Triple-A) manager to bench coach.
In over four seasons at the helm in Cincinnati, Price posted a record of 279-387 and failed to reach the playoffs.
The Reds never won more than 76 games in a single season during his tenure, and they won fewer than 70 in each of the 2015, 2016 and 2017 campaigns.
He has a career record of 662-824 and most recently managed the Nats from 2009 through 2011.
In his 12 seasons as a manager, Riggleman's only playoff appearance came with the Cubs in 1998, but they were swept in the National League Division Series.
The Reds have been trending downward since last making the playoffs in 2013, which marked Dusty Baker's final year as the manager.
Price was handed the keys to a car starting to break down, and he held it together as best he could for one year before it completely fell apart in 2015 with the smoke still rising in 2016, 2017 and 2018.
While another managerial job likely isn't in Price's immediate future, he still has value in Major League Baseball since he served as a pitching coach for the Seattle Mariners, Arizona Diamondbacks and Reds from 2000 through 2013.