The first Wednesday at Roland Garros is traditionally known as kids' day.
The 18th seeded Australian downed German veteran Philipp Kohlschreiber 6-3, 7-6 (7/4), 6-3.
Murray, who was runner-up at Roland Garros previous year, has been struggling in 2017 and looked uncomfortable at times during the second set.
Stan Wawrinka is safely through to the second round after a straight sets win over Jozef Kovalik of Slovakia.
Wawrinka started his clay season poorly before emerging with a title at the Geneva Open last week.
The 18th seed fired down 20 aces and 40 winners to register a 6-3, 7-6 (4), 6-3 victory over the experienced Kohlschreiber in a thrilling opening-round clash that lasted nearly two hours. "Why not? She is a more capable clay court player than most people think and when you consider the big hitters that have won in the women's game, Sharapova twice in the last few years and Muguruza last year, Venus is definitely one of the possibilities".
"All I can speak of are the players that I play against, and they play wonderful every time".
"You know, to just hear a guy in the back of the court just give me some positive things to think about - I get pretty internal at times, and when he's telling me to focus on things, I kind of just think tactically".More news: Super Bowl hero White not taking role for granted
The other seeded American man in action Tuesday, No. 27 Sam Querrey, lost to Chung Hyeon of South Korea 6-4, 3-6, 6-3, 6-3.
All seemed well once he made it out to Court 6 on Tuesday, though.
Nicolas Almagro won a tight fourth-set encounter over Marcos Baghdatis while Paolo Lorenzi, Karen Khachanov and hometown hope Jeremy Chardy all advanced.
The death of Del Potro's grandfather, which prompted his withdrawal at Estoril, left him short of practice on dirt courts, but a run to the Rome quarter-finals suggests the 2009 US Open champion could get amongst the frontrunners over the coming fortnight.
Nara took her first break point to make a dent in the Williams serve, but the 36-year-old broke right back.
Kyrgios responded with: "If I was speeding and you don't catch me, where is the evidence?" I don't feel like my level is a problem.
"I have obviously been struggling physically and obviously not having matches on the clay and not feeling that confident and I saw the draw and I thought it was going to be very tough".
(AP Photo/Michel Euler). Venus Williams of the USA serves against China's Qiang Wang during their first round match of the French Open tennis tournament at the Roland Garros stadium, in Paris, France.