The victory made the 27-year-old just the second Monegasque, after his half-brother and coach Benjamin Balleret, to reach the Monte Carlo Masters third round.
It also marked his second win over a top-five ranked opponent following his triumph over 24-time Grand Slam champion Novak Djokovic en route to his maiden ATP title at the Shanghai Masters last year.
"If someone had told me that my first top-five win of the season, second after Shanghai, would be here on a night session, on the centre court that I've been hitting on since I'm six years old, I wouldn't have believed it," Vacherot said on court.
"Maybe people don't know that I love clay. I grew up playing here for 18 years before going to college and learning how to play on hard courts. But this is where I learned how to play tennis.
"Let's say I needed a set and a half to get on it in the first round. And now my game is back."
Vacherot, who rocketed from number 204 in the world to number 40 after his win in Shanghai and also reached the third round of the Australian Open this year, takes on Poland's Hubert Hurkacz later on Thursday.
