The fourth-seeded Spaniard surged to take the opening set inside 45 minutes but had to work harder in the decisive set against Schiavone, the 2010 champion.
Muguruza was broken early in the second set before recovering at Roland Garros. Schiavone saved three match points before her forehand volley went wide.
"I'm happy that I managed to play, to be kind of composed out there," Muguruza said afterward. "I wasn't sure how I was going to react again on the center court, playing against an ex-champ.
"I found a balance, even though some moments were difficult to overcome. I knew at some point she was going to come up with some great shots."
The 36-year-old Schiavone's exit marks her final appearance in Paris, the veteran having announced she will retire at the end of the season.
After taking a 3-2 lead in the first set, Muguruza won 15 points in a row and broke Schiavone five times.
With the exit of top seed Angelique Kerber on Sunday, Muguruza is the leading seed remaining in the top half of the draw.
The last woman to successfully defend her singles title at Roland Garros was Justine Henin a decade ago.
Muguruza paid tribute to the retiring Schiavone.
"She has been on tour for such a long time, when I look back on some videos, I heard her name since I'm ... I don't know how old," the 23-year-old Muguruza said. "She's fitter than most of the players.
"Today I think it was just a tough match for both of us ... because we kind of love it here. I don't see myself playing at 36. She has a spectacular body, to be able to do that."
Schiavone admitted a slow start cost her the match, but she was pleased with her recovery.
"The first three games you could see that I couldn't put one ball in," Schiavone said. "And then I say, 'Wow, I feel like 15-years-old.' I say, 'Oh, come on. It's 18 times that you play here.' ... Anyway, I'm proud of what I did."
Muguruza next will face Estonia's Anett Kontaveit, who beat Monica Niculescu of Romania 7-5, 6-1.
No. 11 seed Caroline Wozniacki of Denmark survived a second-set scare to beat Australian wild card Jaimee Fourlis 6-4, 3-6, 6-2 and reach the second round. The 17-year-old Fourlis is ranked 337th in the world and was appearing in only her second Grand Slam.
No. 18 seed Kiki Bertens of the Netherlands recovered to beat Australian Ajla Tomljanovic 4-6, 6-1, 6-1.