The match was eagerly anticipated as Murray made his clay-court comeback at the venue that left his hip shattered.
It was the semi-finals of the French Open 2017 where former finalist, Murray, took on former champion Wawrinka, which went to five grueling sets.
The Swiss has also endured battle scars from the encounter, needing two operations on his knee to save his career.
The Briton has had a more arduous comeback trail requiring hip surgery followed by a potentially career-saving hip-resurfacing operation.
The irony of this first-round blockbuster was the experienced duo found themselves back on Court Philippe Chatrier after a long three and half years but with no crowd due to Coronavirus restrictions.
Both players have snared three Grand Slams each from the big three of Roger Federer, Rafael Nadal, and Novak Djokovic, over the years, but it is fair to say both are now in the twilight of their careers.
The former British number one held serve comfortably in his opening service game but this was as good as it got as the Swiss powerhouse seized the next six games including a triple break to clinch the first set 6-1.
The former Australian Open, French Open, and US Open champion didn't need to break a sweat as Murray appeared rusty on the clay having had no practice on the surface coming into the French Open.
The first break was a result of poor shot selection from the two-time Wimbledon champion mixed with a cluster of unforced errors having been locked at deuce, eventually gave Wawrinka the break.
Having won his only Masters 1000 on clay, the 2014 Monte Carlo Masters, Wawrinka showed the movement and guile that helped take him as high as world number three.
The world number 17 put away a stylish overhead smash before an ace sealed an easy hold of serve.
The second break of serve followed as a Wawrinka planted an easy forehand winner into the corner to go 4-1 up and cruise towards the opening set.
Murray, known as one of the best returners in the world, was unusually sloppy as he even struggled to put Wawrinka's slow second serves back into play.
A third break soon followed as Murray looked off the pace gifting the Swiss a trouble-free opening set to his French Open campaign.
The second set was a much better effort from the former world number one as he matched Wawrinka's hold of serve but the Swiss kept his nose in front to maintain the pressure on the 33-year-old.
The pivotal moment in the second set came in the sixth game as Wawrinka's powerful baseline play, reminiscent of that which took him to the title in Paris all those years ago, broke Murray's resolve as a wayward forehand gifted the break putting the Swiss 4-2 up.
The break was consolidated with a beautiful topspin drop-shot by Wawrinka in arguably one of the more exciting moments of the match.
A narrow hold of serve from the Brit kept him in the hunt, but a merciless forehand winner into the empty corner by the Swiss took him two sets to love up.
Wawrinka kept up his dominance in the third set as a classy overhead lob, returned by the Brit, was met by another outrageous top spin drop-shot.
Murray, normally the master shot maker, was being given the run around on Chatrier by a much more polished clay-court specialist.
At 40-0 up, Murray looked to be cruising before a range of sloppy errors gifted Wawrinka another break.
Murray would go on to at least secure his next two service games but still trailed 4-2. Wawrinka was not to be denied though as a stunning backhand pass gave him the double break.
The Swiss capped off a resounding victory with an ace to move into the second-round within just an hour and 37 minutes.
Next up for the three-time Major champion is Germany's world number 66 Dominik Koepfer who is in decent form having made the quarter-finals of the Italian Open, even taking a set off eventual winner Novak Djokovic.
The Swiss will be keen to avoid an upset and back-up this one-sided and complete performance.
As for Murray, he is left to lick his wounds and must ponder where his season will go next, in terms of his next tournament entry, but also if he will ever go deep in a Grand Slam again.