Rome: Top seed Novak Djokovic and number two Andy Murray produced no-drama victories, with the Serb beating Stephane Robert 7-5, 7-5 while Murray put out Kazakh Mikhail Kukushkin 6-3, 6-3.
"Today was an extremely difficult match," Djokovic said. "Conditions were very tough, he was very unpredictable with his shots.
"Obviously he didn't have anything to lose, so he was going for some shots that were amazing.
"It wasn't easy for me to find my way through the match. When it mattered the most, I managed to make him play an extra shot and pull this one through."
Rafael Nadal continued his recent good form, beating Philipp Kohlschreiber 6-3, 6-3.
Australian Nick Kyrgios picked up another big win in an excellent season so far, putting out tenth seed Milos Raonic 7-6 (7/5), 6-3.
French 11th seed Richard Gasquet beat Andreas Seppi 6-3, 6-4.
Earlier, Roger Federer eked out a 6-3, 7-5 victory over Alexander Zverev but the Swiss later admitted that he was fully expecting to lose.
"I'm cautious but extremely happy - I was expecting to lose in straight sets today," admitted the 17-time Grand Slam champion, who withdrew last week from Madrid with back pain.
"That was the mindset going in. To win in straights is actually a really big surprise to me.
"I only decided after the warm-up that I was actually going to play. For me it was a big match on many levels."
The 89-minute match was the first for the 34-year-old Swiss since losing a Monte Carlo quarter-final to Jo-Wilfried Tsonga nearly a month ago.
Kerber, Azarenka and Halep dumped out
In women's second-round play, Eugenie Bouchard handed second-seeded Australian Open champion Angelique Kerber a 6-1, 5-7, 7-5 defeat, her second straight in an opening match after losing last week in Madrid.
"In the first one-and-a-half sets I was completely not playing my game and I was completely not on the court," the German said.
"I was just trying to fight back. I was not playing my best tennis. But of course I was fighting and the third set was really close. At the end she played good and won the last point."
Spanish third seed Garbine Muguruza crushed Russian Ekaterina Makarova 6-1, 6-0 while Madrid quarter-finalist Irina-Camelia Begu of Romania upset injured fourth seed Victoria Azarenka 6-3, 6-2.
The Belarusian withdrew with lower back pain last week from Madrid.
"I was trying but it didn't work," Azarenka said. "The back is not good right now. I'm very disappointed obviously with that.
"I thought I was okay and was ready to play and came back, so I'm just disappointed. We'll see what happens."
Australian Daria Gavrilova dispatched Madrid champion Simona Halep, seeded sixth, 6-3, 4-6, 6-3.
American Madison Keys knocked out fifth seed and two-time quarter-finalist Petra Kvitova 6-3, 6-4, while Misaki Doi saw off French Open finalist Lucie Safarova 6-3, 7-5.
American 7-time major winner Venus Williams bowed out after a marathon defeat to Timea Babos that lasted nearly three hours.
Updated Date: May 12, 2016 13:26 PM