The 30-year-old world number one, bidding to reach a second successive final and go on to end Britain's 82-year wait for a men's champion in Paris, suffered a 6-7 (6/8), 6-3, 5-7, 7-6 (7/3), 6-1 loss in a four hour 34 minute epic.
But Murray insisted that there were plenty of positives to take into his Wimbledon title defence after arriving in France with a fever and in mediocre form.
He has also endured a season punctuated by an elbow injury, shingles and flu.
"I'm proud of the tournament I had. I did well considering. I was one tiebreak away from getting to the final when I came in really struggling," said Murray, the runner-up to Novak Djokovic 12 months ago.
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"Maybe the lack of matches hurt me a little bit in the end today. It was a very high intensity match.
"I do feel like having an event like this can give me a boost, and hopefully have a strong grass court season."
He needed four sets to get past Andrey Kuznetsov and Martin Klizan in the first two rounds.
Then, in what was expected to be a third-round ambush, he sailed past Juan Martin del Potro in straight sets and was similarly at ease against Karen Khachanov in the last 16.
However, in the quarter-finals, he dropped the first set against Kei Nishikori before his greater stamina proved decisive.
That stamina eventually deserted him against Wawrinka who he defeated in four sets in the semi-finals last year.
The top seed was rock steady with 36 winners and the same number of unforced errors but Wawrinka, the oldest man to make the final in 44 years, employed his big swinging game to perfection.
Murray slipped 0-5 and triple break down in the final set, a harsh indicator of the sudden shift in the balance of power.
"I lost a little bit of speed on my serve which wasn't allowing me to dictate many points on my own serve," explained Murray as Wawrinka went into overdrive to record a 10th successive win on clay.
"He hit some great shots in the fifth, but I didn't keep the score close enough to sort of put him under pressure.
"Physically, I didn't feel my best at the end.