Gauff has already beaten Top 20 players three times before—Kiki Bertens last year, Naomi Osaka and Aryna Sabalenka this year—and at times it looked like she was going to add the No. 17-ranked Muguruza to her resume after winning the second set and building a 2-0 lead in the third.
But Muguruza found her range when she needed it, getting the break back and eventually winning six of the last seven games of the match, clinching victory after Gauff missed a forehand into the net.
“It was a tough match. I’m looking forward to tough matches,” Muguruza said. “The first set was tight. It could have gone both ways, but I’m happy it went my way after a good fight. In the second set I didn’t take the opportunities I had, and she was there the whole time. The third set was a battle again, but I managed to be solid, play my game and take the opportunities I didn’t take in the second set.
“She’s a great competitor. She can play very well—she’s proven it, she’s beaten many good players.”
The Spaniard, a two-time Grand Slam champion at Roland Garros in 2016 and Wimbledon in 2017, is playing her second event back, falling to Tsvetana Pironkova in the second round of the US Open.
“I’m just thinking to leave from Rome with the trophy, or just playing as many matches as possible. I don’t have that many expectations after not playing for a long time, and the US Open was short, so I’m just being here enjoying it as much as I can, trying to play every match like it was the last one.”
Up next for the No. 9-seeded Muguruza will be No. 7-seeded Johanna Konta, who came out of the blocks swinging, hitting 22 winners to just 12 unforced errors to beat Irina-Camelia Begu, 6-0, 6-4.
Muguruza and Konta are tied 2-2 head-to-head, with all four previous meetings going three sets.
There were mixed results for the other women’s seeds in early action on Thursday, with No. 12 seed Marketa Vondrousova advancing but No. 8 seed Petra Martic and No. 14 seed Anett Kontaveit going out. Martic dug out of a 6-3, 5-1 hole but ended up falling to Yulia Putintseva, 6-3, 6-7 (2), 6-4, having also lost to her fourth round at the US Open, and Kontaveit fell to Svetlana Kuznetsova, 4-6, 7-5, 6-3.
There were early upsets on the men’s side, too: No. 7 seed Fabio Fognini lost to Ugo Humbert, 7-5, 7-6 (4); No. 9 seed Andrey Rublev fell to Hubert Hurkacz, 7-6 (6), 3-6, 6-2; and No. 13 seed Milos Raonic was ousted 7-6 (3), 4-6, 6-2 by Dusan Lajovic, who will now face Rafael Nadal in the next round.
Also among the early men's winners was No. 12 seed Denis Shapovalov, who won six of the last seven games of his match, rallying from 3-0 down in the second set to beat Spanish qualifier Pedro Martinez, 6-4, 6-4. Shapovalov is fresh off reaching the first Grand Slam quarterfinal of his career at the US Open, becoming the first Canadian man in the Open Era to reach the last eight there.
"Of course it's very tough,” the 21-year-old told ATPTour.com. “Especially after the Grand Slam, your body just kind of naturally wants to relax. Going into a match here is definitely a little bit difficult, but I'm really happy with the way I have been able to maintain my level and maintain physically.”