Tsitsipas' title defence ended by Fritz in Monte Carlo
Second seed Tsitsipas was on a 12-match winning streak in the principality but slumped to a 6-2, 6-4 loss in only 70 minutes.
Fritz will face Russian Andrey Rublev on Saturday in the last four as he attempts to reach the final of a clay-court event for the first time.
"I thought my level today was very high. I think I played a very good match. Beating him here gives me a lot of confidence," Fritz said.
"It has given me the reassurance I need to know I can play well on clay.
"I seemed to play well on the big points. I took my chances."
Fritz's win was his first against Tsitsipas after three previous defeats by the Greek, including a five-set thriller at the Australian Open last year.
The world number 10 -- who reached a career-high ranking of fifth earlier this year -- is into his third Masters semi-final, with the other two both coming at Indian Wells where he won the 2022 title.
Australian Open runner-up Tsitsipas had been the favourite to win the tournament after Novak Djokovic's shock last-16 exit at the hands of Lorenzo Musetti on Thursday.
But he made a poor start against Fritz, falling 4-0 behind in the opening set and was never able to change the momentum.
Eighth seed Fritz secured the crucial break in the ninth game of the second set and served out the victory.
"I just seemed off. My serve was not working very well today, and against opponents like Taylor, you have to serve well," said Tsitsipas.
"I was aware of that during the match. I just couldn't find the rhythm."
Tsitsipas has struggled for form and with a shoulder injury since his loss to Djokovic in the Australian Open final.
The world number three is still waiting for a first Grand Slam title but will be among the main contenders for the French Open next month.
"I would have never pictured myself dealing with such an injury," added Tsitsipas.
"It would have been perhaps the last thing that I could think of in terms of injury with tennis. It's probably the worst injury that I've had on the tennis court so far."
Rublev sees off Struff
Rublev, who lost to Tsitsipas in the 2021 final, booked his place in the semi-finals with a 6-1, 7-6 (7/5) win over German qualifier Jan-Lennard Struff.
The fifth seed won six straight games after being broken in the opening game and clinched victory in a tense second-set tie-break.
Rublev has lost four of his previous six meetings with Fritz, but the pair have never played each other on clay.
"Doesn't matter the surface. It's tough," said Rublev.
"You know, when the guy returns full power to you, you need a couple of shots to start the rally, because if he returns well, you're in danger."
Later on Friday, Daniil Medvedev will take on Holger Rune before Musetti faces fellow Italian Jannik Sinner in the other quarter-finals.