Djokovic, beaten in the final by Britain’s Andy Murray last year, will now face Juan Martin del Potro in the quarters after the unseeded Argentinian’s third round 7-6 (7/4), 6-3 win over Japanese seventh seed Kei Nishikori.
Rafael Nadal, enjoying his best season on clay in two years, will look to book his place in the last eight later when he meets American Jack Sock, seeded 13th.
The Spaniard, a seven-time champion in Rome, swept Djokovic aside in the semi-finals of the Madrid Masters last week before going on to secure the title. But French Open champion Djokovic said: “I’m getting closer, I feel like today’s match was one of the better ones I’ve played on clay this season, and in the past couple of months.
“It’s coming at the right time, we’re getting closer to Roland Garros. All the players are looking to raise their game for Paris.
“I’ve been doing my best to optimise my game... right now, as days are passing by, I feel more comfortable on the court.”
Another playing looking to up his game for the French Open is 2015 champion Stan Wawrinka but the world number three from Switzerland said a lack of confidence was to blame for his shock 7-6 (7/1), 6-4 defeat to big-serving American John Isner, who is ranked 24th in the world.
“When you lack confidence and rhythm, against opponents like (Benoit) Paire and Isner, it’s not ideal,” said Wawrinka, who had beaten Frenchman Paire 6-3, 6-4 on Wednesday.
“I had some chances to break him at the start of the match, but I didn’t push him hard enough.
“My game and my physical condition are there. But confidence, you can lose it quickly. But I’ll keep fighting.”
Isner, meeting Wawrinka for the first time in six years, will now meet Marin Cilic after the sixth seed from Croatia beat Belgian David Goffin, the ninth seed, 6-3, 6-4. “I went out there with the belief that if I played well and executed my game plan that I could walk off that court with a win,” said Isner.
But beating Cilic, he said, might not be so straightforward.
“Yeah, he has been a bit of a thorn in my side. The last time we played I won in Paris last year, the indoor tournament in Paris,” added Isner.
“It should be a close match. Not much has separated us when we have played each other in the past.”
In the women’s tournament, Venus Williams overcame determined Briton Johanna Konta to win their third-round clash 6-1, 3-6, 6-1.
In the absence of sister and defending champion Serena, she will now meet Spain’s Garbine Muguruza on Friday for a place in the semis and a possible match-up with Czech second seed Karolina Pliskova.
Williams, competing in Rome because “I still have a lot to give”, was more circumspect about her chances of emulating Serena by winning Roland Garros.
“It’s so different when you’re talking about it or when you’re playing it,” she said.
“When you’re playing it, it’s a lot of work. There is not even one point that is given.
“My whole thing about it is to try to win my match no matter who I play against. I hope to have more luck and more skill.”
Russia’s Svetlana Kuznetsova, the seventh seed, won’t be going so far after she exited following a 2-6, 7-5, 6-4 defeat to Australian qualifier Daria Gavrilova.
Gavrilova will meet Dutch 15th seed Kiki Bertens after she beat unseeded Russian Ekaterina Makarova 7-6 (7/3), 6-1.