Flailing Frankfurt sack coach Toppmoeller
Junior coaches Dennis Schmitt and Alexander Meier will take over the club on an interim basis.
In a statement, Frankfurt said the "decision is the result of a comprehensive sporting and structural analysis".
Toppmoeller took Frankfurt to third spot and Champions League qualification last season, the Eagles' best result in three decades.
The club sold star striker Hugo Ekitike to Liverpool in the summer and have fallen back to earth this campaign, winning just one of their past nine in all competitions.
Frankfurt sporting director Markus Kroesche said "due to the recent decline in performance, we need a new sporting impetus."
Frankfurt are five points behind the top four in seventh in the Bundesliga, and are down in 30th place in the Champions League league phase, winning just one of their six matches.
Frankfurt's ambitions have been undone by a shaky defence. No club has conceded more than Frankfurt's 39 goals in the league this season.
Toppmoeller said he "would have loved to continue working with the team" but accepted the decision, saying he "wished Frankfurt calmer and more successful times."
After a disappointing 3-3 draw at Werder Bremen on Friday, Kroesche criticised Toppmoeller and the team.
"It's always the same mistakes. We can't continue like this," Kroesche said.
"We've had the same issues plague us for 17 or 18 games now. We're conceding incredibly easy goals, we're far too frantic in possession – and we have no structure."
Toppmoeller took over from now-Crystal Palace manager Oliver Glasner in 2023 and took Frankfurt to sixth, before last season's third-place finish.