Britain’s Murray, 37, has said this year is likely to be his last one on tour and avoided surgery on an ankle injury in order to return to Roland Garros.
But his lack of court time was evident in a 6-4 6-4 6-2 loss to the 39-year-old Swiss.
It was the former world number one’s first appearance on the Paris clay since a first-round defeat in 2020, and only the second since a brutal loss in the 2017 semi-finals – both also at the hands of Wawrinka.
“It was always going to be tough, tough match. Stan has, over the years, played brilliant tennis on that court,” Murray said.
“I was expecting him to play very well. I think he did that. He gave me very few opportunities.
“I wish I could have done a little bit better.”
Murray’s exit on day one in Paris came after Jack Draper lost to Dutch qualifier Jesper de Jong as the British campaign got off to an inauspicious start.
Draper, 22, is 35th in the world but was beaten 7-5 6-4 6-7 (3-7) 3-6 6-3 by 176th-ranked De Jong.
Murray and Draper were the first of six British players to step out on to the Roland Garros dirt, with Katie Boulter, Cameron Norrie, Dan Evans and Harriet Dart opening their campaigns on Monday and Tuesday.
Murray’s French Open is not over yet as he has entered the men’s doubles alongside Evans.
