This has proved to be Fritz’s breakthrough moment in his 33rd Grand Slam appearance.
He lost to Novak Djokovic in the US Open quarter-finals in 2023, twice lost in the last eight at Wimbledon in 2022 and July this year and suffered defeat in the Australian Open quarters in January.
After sharing two tight sets, the crucial moment came deep in the third when Zverev looked to have the momentum, having recovered an early break.
He missed a straightforward backhand on break point at 4-4 which allowed Fritz to hold and then the fourth seed offered up three forehand errors to fall 0-40 behind.
Zverev fought off those three set points but Fritz eventually broke through at the fifth attempt.
Zverev will feel he had his moments but Fritz won by being able to neutralise Zverev’s booming first serve and remain the more solid with the finish line in sight.
He gained the initiative in the fourth-set tie-break by taking the first point on the Zverev serve and won a gruelling 24-point rally for the second break and a 5-2 lead.
Fritz faltered momentarily, pushing a nervous forehand wide, but Zverev offered up two more errors to seal the result.
Zverev, seeking a third US Open semi-final and his first Grand Slam title, was unusually flat in the final set and complained throughout about his racquet.
“I know the crowd would really want to see me play Frances so we get an American in the final,” Fritz added.
“That could be crazy, so I guess we’ll see what happens – but either way I’ll be ready to go.”
Britain’s Jack Draper is among those remaining in the top half of the draw. He plays Alex de Minaur in the quarter-final on Wednesday.