The 37-year-old American survived a first-set scare before defeating Russia's Vitalia Diatchenko 2-6, 6-1, 6-0 to reach the second round, AFP reported.
"Yeah. It is a lot to carry, but so is being Serena Williams," she said after the match.
The American, who is attempting to equal Margaret Court's all-time record of 24 Grand Slam titles, racked up her 800th career main draw win with her victory in front of a half-full Court Philippe Chatrier.
After dropping the first set, she was in danger of suffering just the second opening round defeat of her Grand Slam tournament career.
But normal service was quickly resumed as she racked up 12 of the last 13 games.
"You know, I have been dealing with a lot, and then I just got nervous out there and I stopped moving my feet.
"There were like concrete blocks on my feet. I was, like, 'You gotta do something'."
Williams, the 2002, 2013 and 2015 champion in Paris, won her most recent major at the Australian Open in 2017 while pregnant.
She returned to Grand Slam tennis after giving birth to her daughter at Roland Garros in 2018, making the last 16 where she had been set to resume her bitter rivalry with Maria Sharapova.
An arm injury torpedoed that meeting and stalled her assault on a fourth title in Paris.
Defeat in the 2018 Wimbledon final and US Open championship match, where her now-infamous meltdown overshadowed Naomi Osaka's title triumph, followed her Paris heartbreak.
Her Australian Open campaign in January ended in a quarterfinal loss to Karolina Pliskova despite having led 5-1 in the final set and holding four match points.
Since Melbourne, Williams had been unable to finish the three tournaments she had entered – retiring in the third round of Indian Wells and withdrawing after winning a round in Miami, and after winning one round in Rome due to a right knee injury.