Fish, the top seed in the tournament and ranked ninth in the world, was playing for the first time since pulling out of Davis Cup competition against France for what he called a health issue.
"What happened a couple of weeks ago scared me," Fish said. "Obviously, I'm not over it. I think anyone could see I wasn't myself."
Second-seeded John Isner had 16 aces and recovered from a slow start for a 6-7 (3), 6-4, 6-2 victory over Horacio Zeballos of Argentina. Isner won 76 percent of his first serves and his big serve got stronger as the match went along.
"It was difficult to loss that first set, but I told myself to keep on my serve and that's what happened," Isner said.
The 136th-ranked Russell knew he had a great opportunity.
"In the beginning, I thought he was playing pretty well and it was neck and neck and then his game definitely deteriorated big time," Russell said. "I just tried to ride the wave."
Fish hit only 52 percent of his first serves and had five double-faults.
The 33-year-old Russell beat a top-10 player for the first time in his career. He double-faulted once and hit on 70 percent of his first serves.
"I was trying to take advantage of my service game and I took advantage of a lot of his unforced errors," Russell said. "It turned out great."
Russell said he was surprised that Fish played so quickly.
"He was playing very quick between points," Russell said. "It was unusual. When I'm up a break usually you'll take a little more time but he was kind of rushing through. I wasn't going to stop him. I wanted to keep the momentum going."
Fish said he wasn't certain about his next move.
"I'll get with family and try to sort some things out," Fish said.
South Africa's Kevin Anderson, seeded fifth, had 13 aces and saved eight of 10 break points to edge Sam Querrey 7-6 (3), 3-6, 7-6 (2) in the second round. After taking a 6-2 lead in the final tiebreaker, Anderson won it at the first match point.
"I had to dig deep to get through that first set," Anderson said. "I played well in the tiebreaker. I thought I played better than yesterday. I tried to be aggressive and I was able to do that."
Fourth seeded Juan Monaco of Argentina defeated Tatsuma Ito of Japan 6-3, 6-3. Monaco is 8-2 on clay this year and reached his third quarterfinal of the season. He will play Anderson in the quarterfinals Friday.
"Little by little, I played better and I think I deserved to win," Monaco said. "Hopefully, I will play better tomorrow."