Serra ousted the second-seeded Verdasco, hampered by a sore ankle, 6-2, 7-6 (4). Gremelmayr took a 7-5, 7-5 victory over No. 4 seed Lopez.
Sixth-seeded Mardy Fish came back strong after losing the first set to take a 6-7 (5), 6-1, 6-0 win over Vince Spadea.
Top seed Andy Roddick opens play on Thursday night against Dusan Vemic after Donald Young, a 19-year-old who upset defending champion Tommy Haas in the first round, faces Marc Gicquel in an afternoon match.
Verdasco, No. 12 in the ATP rankings, double-faulted 10 times, including the final point of the match.
After the defeat, Verdasco limped into the interview room and was gracious in his comments about Serra and hesitant to use his tender right ankle as an excuse.
"He played very good," said Verdasco, from Spain. "When I played short, he made long shots, hit good winners. Maybe I was not 100 percent, with the ankle. I tried."
Serra, a Frenchman ranked No. 75, said Verdasco was the best player he has beaten this year.
"I felt very good," Serra said. "Hopefully, I will be here through the weekend."
Gremelmayr saved seven of eight break points in his win over Lopez.
"It was a tough match. It's a very good win for me," said Gremelmayr, a German ranked 89th.
Lopez, from Spain, is No. 26.