The US Open champion and world number two started his clay court season against Eduoard Roger-Vasselin, securing a two-set second-round win.
But he had no answer to the power of Wawrinka in a 6-1 6-2 defeat which lasted less than an hour on Monte Carlo's Court Central.
After holding serve in the opening game Murray had a break point in the second but was the first to lose his delivery in the next as Wawrinka edged 2-1 ahead.
Murray was 15-40 down when his opponent hit a forehand service return well out.
But Murray netted the next point to drop his serve and trail the Swiss.
Wawrinka consolidated the break by winning his serve to 30 to lead 3-1 when Murray hit a backhand return long.
In the next game Murray left a backhand passing shot from Wawrinka which just caught the line and after a double fault was again 15-40, hitting the next point out on a volley at the net to trail 4-1.
Wawrinka held to lead 5-1 and leave Murray serving to stay in the opening set.
A double fault by Murray was hardly the ideal start to the seventh game and when he netted a forehand on the next point
Wawrinka was well on his way to the first set.
A netted backhand gave Wawrinka three set points but Murray dug deep to claim the next point with a well-hit forehand which his opponent could not return.
But a wide backhand from Murray gave his opponent the set by a 6-1 score.
Wawrinka's domination was typified by a backhand cross-court which put him 30-0 ahead in the first game of the second set and he followed that with an ace and a strong serve down the middle which Murray could not return in.
Murray opened the second game with a fine drop volley to win the first point, taking the next two courtesy of errors from Wawrinka.
A high bouncing serve from Murray saw Wawrinka hit his return out and the Briton levelled at 1-1.
Wawrinka held to love as Murray continued to struggle but he showed resolve to level at 2-2 after saving another break point.
A comfortable hold by Wawrinka was followed by further struggles for Murray on his serve.
A forehand down the line saw Wawrinka set up another break point which he claimed when Murray volleyed long at the net for the Swiss to lead 4-2.
Wawrinka opened game seven with an ace which just clipped the line, going on to hold to leave Murray serving to stay in the match.
Wawrinka hit a service return long to fail to take the first of two match points but when Murray netted a forehand on the next the Swiss had triumphed with surprising ease.
Murray admitted his poor start to the match had allowed Wawrinka to take charge.
"When I started making a lot of errors he was able to dictate all of the points from there," Murray said in the post-match press conference.
"If you take your foot off the gas you don't give any power in your shots to dictate the points to your opponent."
Murray conceded he normally needed time to settle into the clay court season and today's performance reflected that.
"I've played some good tournaments here but it does take me time to feel comfortable on the surface. I need matches against top players to see what's going wrong and going right and the things I need to work on to get better."
Murray admitted the manner of his defeat had left him disappointed but he will aim to use it as a spur to improve for his next outing in Madrid in two weeks, indicating that he would miss the next tournament in Barcelona.
"It's disappointing, no one wants to lose matches like that. Hopefully I can use it as motivation to improve because I really need to do a lot of work.
"I need to work really hard over the next two weeks to get ready for Madrid."