The world number four, who reached the last eight in Monte Carlo for the third time, was forced to battle exceptionally hard against his doughty opponent who looked inspired as the first set appeared to be perfectly poised.
But at 5-5 and 30-0, Benneteau took a terrible fall, stretching for a forehand behind the baseline, and badly injured both his right ankle and wrist.
Benneteau attempted, albeit fleetingly, to battle on after lengthy physio treatment, but his intentions to continue were futile as he was unable to play on and he was forced to present his opponent with an early handshake.
Murray, who now boasts a 3-0 head-to-head record over the Frenchman with wins in Cincinnati and Wimbledon previously, was looking to continue to the fine form he showed in his second round match against Viktor Troicki at the start of his clay-court campaign.
It was a tough start for the British number one as he was forced under the cosh as Benneteau produced a series of crisp groundstrokes to take the game to an extended deuce, but eventually Murray came through with a blistering forehand closing out the hold.
A near replica of the opening game followed in the second as long rallies took it into a seemingly interminable deuce before Murray pounced with a powerful backhand to force the error and seal the break of serve.
But Murray’s advantage did not last long as Benneteau broke straight back at the fifth opportunity as the Frenchman was rewarded for his patience and tenacity with his opponent eventually going wide with a backhand to lose the game.
The quality of play was sensational as both players traded blows from the back of the court, and the high standard was unwavering on Court Central as neither player was able to stamp their authority on proceedings in a hard-fought opening set.
Benneteau, who had already achieved his best ever result in Monaco after eight previous appearances in the main draw, continued to frustrate his opponent as he played with real craft and guile, clearly buoyed by the support of the crowd.
It was at 5-5 with the set finely poised that Benneteau badly injured both his right ankle and wrist as he lunged outwide to retrieve a forehand, and a lengthy injury time-out ensued as the Frenchman was treated on court.
Murray proceeded to close out his service hold to love, but the Frenchman was clearly unable to continue playing and was forced to retire as he sought further treatment for his injuries off court.
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