Greek second seed Tsitsipas, who triumphed at the Monte Carlo Country Club in the last two editions, was never in the mix against Fritz, who is targeting his second Masters title after winning in Indian Wells last year.
"I just seemed off. My serve was not working very well today, and against opponents like Taylor, you have to serve well,” Tsitsipas said.
"I was aware of that during the match. I just couldn't find the rhythm. I am much better than this and I'm disappointed I was not able to show my game today.
"I tried to fight in the second set. It's a good lesson. It's not a happy day for me, but it's a good lesson."
Eighth-seeded Fritz raced to a 4-0 lead in the opening set, which he wrapped by winning his service game to love.
Tsitsipas improved slightly in the second set, only for Fritz to break decisively for 4-3 with a winner. He then held firm to secure the win and set up a semi-final meeting with Andrey Rublev (25).
The Russian overcame some second-set nerves to dispatch German qualifier Jan-Lennard Struff (32) 6-1 7-6(5).
Rublev lost the first game on his serve before bagging six in a row in a quick opening set, but Struff, the world number 100, found his stride in the second as the fifth seed showed signs of nerves.
Rublev broke for 4-3, only for Struff to break back in the following game and force a tie-break, in which the Russian regained his composure to prevail on his second match point.
In the other half of the draw, Denmark's Holger Rune (19) tormented third seed Daniil Medvedev (27) with passing shots and drop shots to advance with a 6-3 6-4 victory.
Rune, who proved a sensation at last year's French Open when he reached the quarter-finals, dropped only six points on serve in the opening set and converted his only break chance in the second.
He will next meet Jannik Sinner (21), who dismantled Lorenzo Musetti (21) 6-2 6-2 in an all-Italian clash.
Seventh seed Sinner saved all five of the break points he faced against Musetti, who beat world number one Novak Djokovic on Thursday.
