Friday's other winners were the top three seeds in the ATP 250 clay-court event - Fabio Fognini, Mikhail Youzhny and Roberto Bautista Agut.
Rosol only managed to land just over half of his first serves against the world number 24, but showed good resolve to rescue six of the eight break points Lopez managed to open up in a 4-6 6-3 7-6 (7-4) win.
Though the Spaniard fired 16 aces to the Czech's 11 and enjoyed a superior first-serve percentage, Rosol emerged triumphant and will face Youzhny in the final four.
Youzhny himself was a relatively comfortable 7-6 (7-2) 6-2 winner over eighth seed Federico Delbonis.
The Russian, champion of the event in 2002, opened up 15 break points against the Argentine, but only converted two of them.
Defending champion Fognini also won through in relative comfort, beating Santiago Giraldo 6-4 6-3 in 81 minutes.
The Italian is yet to drop a set in Stuttgart, having beaten Andrey Golubev 6-4 6-4 on Thursday, and believes he is growing into the competition as he prepares to face Bautista Agut.
"I think I played better than yesterday," said Fognini.
"I'm happy I have another opportunity to play in the same semi-final as last year. But I think it will be completely different.
"[Bautista Agut] has improved a lot in the past year. He's in good shape, but me too. I feel great, especially at this tournament. It's going to be a tough match, but I'm ready."
Bautista-Agut sealed his semi-final spot with a marathon 3-6 6-4 7-6 (7-1) victory over compatriot Guillermo Garcia-Lopez.
The third seed will have to overcome a 1-4 head-to-head record with Fognini if he is to reach a second Tour-level final of the season.