The third-seeded Garcia-Lopez rallied from 4-1 down in the first-set tiebreaker, winning six straight points to clinch the set.
Seppi earned the first break of the match for a 3-2 lead in the second, but Garcia-Lopez responded again by winning the next four games. He clinched the win when Seppi sent a backhand into the net.
"This was very emotional. He played good tennis to get to 4-1 in the tiebreaker, and I think it was very important to win the long rally at 4-3,"Garcia-Lopez said. "When I broke back in the second set I think he was very disappointed."
Garcia-Lopez had never defeated Seppi in four previous meetings.
"I have never played good against him, I was not in good shape," he said. "His style is not good for my game, he is solid from both sides. Today I tried to change the rhythm."
The fifth-seeded Italian made 40 unforced errors.
"It was a difficult match. I think he played very good tactically," Seppi said. "Sure it did not feel nice to lose the set after being 4-1 up. At 4-3 we played a long rally ... I was still pretty calm after I lost the set, I was even a break up in the second, but I lost concentration in the middle of the second set."