The seventh seed who lifted his first elite Masters 1000 title here a year ago as he beat compatriot Roger Federer for the title, spent 71 minutes in getting past Monaco.
"I played well, and I'm pleased to be back on clay." said the winner, who broke five times from 14 chances. "It's nice to be defending a title and starting it out like this."
Wawrinka, the 2014 Australian Open winner, was to await an opponent from ninth seed Grigor Dimitrov and Italian Fabio Fognini.
The Lausanne native comes onto the spring clay with a 17-4 match record and titles in Chennai and Rotterdam.
The 30-year-old successfully defended a title for the first time in January, winning Chennai for the second year in a row.
Spanish 16th seed Tommy Robredo crushed compatriot Marcel Granollers 6-1, 6-1 in an early match played under the first clouds of the week at this Mediterranean principality.
Federer, a three-time runner-up at the seaside Country Club, took just 54 minutes to dominate Jeremy Chardy 6-2, 6-1 as the Frenchman sent in a pair of double-faults in the penultimate game.
Second seed Federer then advanced with his third ace on match point a game later.
"Jeremy didn't serve very well, and I felt good on the return," said the Basel native.
"So I was in a lot of the service games when he was serving," Federer said.
"I thought I served well, had a high first serve percentage and was able to control the baseline," he said.
"On clay, things move ahead very quickly, I must say."
For third seed Rafael Nadal, his 6-2, 6-1 second-round success against French wild card Lucas Pouille came as a huge relief after a poor season and just one small South American trophy to hand since winning a ninth Roland Garros title last May.
"I'm glad to be back here and playing on clay," said the troubled Spaniard who improved his record here to 51 wins and just three losses as he moved into the third round.
"It was a tough match, but I played little bit better than what I was doing before."
Meanwhile, Wawrinka came in for a lot of ribbing on social media for his choice of shorts on Wednesday: