Fourteenth seed Flavia Pennetta proved too tough an opponent for Anne Keothavong, who became the first Briton to fall at this year's French Open.
Pennetta came through 6-2 6-2 in one hour and four minutes and goes on to face fellow Italian Roberta Vinci or France's Virginie Razzano in round two.
The result leaves Britain with two women remaining in the singles, Elena Baltacha and Katie O'Brien, both of whom have similarly testing first-round matches.
Keothavong battled hard but Pennetta, a winner of nine WTA Tour titles and recent top-10 player, was able to exert more pressure when it mattered.
It was always likely to be a tall order as Keothavong's only win over the Italian had come 10 years ago, Pennetta winning their other meeting back in 2002.
If you ask anyone in the locker room I think they'd all agree that I'm a better player than my ranking suggests
Anne Keothavong
The Briton, 26, had made it as high as 48 in the world rankings last year before a serious knee injury in the summer put her out of action until Februrary, and facing Pennetta on clay proved too much.
Keothavong refused to be too downbeat after the match, though, telling BBC Sport: "Flavia played a really good match. I don't think I played badly, I just think she was aware that she'd have to play that well if she was going to beat me in the way she did today.
"It's pretty hot out there and the conditions are tough, the court's fast and lively, but I have no complaints.
"Her backhand is fantastic and unfortunately I just couldn't pressure her forehand enough or hit my returns deep enough, but that's what happened."
And the Briton vowed to come back and push her ranking upwards as she continues in her battle to make up for lost time through injury.
"If you ask anyone in the locker room I think they'd all agree that I'm a better player than my ranking suggests - even now three months after coming back from a cruciate ligament injury," she said.
"It's just a case of getting out there and playing as many matches as I can to get my ranking back up. Now I look forward to the grass-court season."
Number One Court can often produce an intense atmosphere but, on a roasting hot day in Paris, the match began with the steep-sided stands half empty as spectators went in search of shade and refreshment after the preceeding men's match.
The sedate surroundings probably did not help Keothavong, who prefers heavy, damp conditions on clay and a touch more life in the crowd.
Pennetta, 28, took the initiative with an immediate break, consolidated by a backhand arrowed down the line which would become a feature of the match.
Urged on by the British contingent in the stands, Keothavong upped her intensity markedly and, after one spectacular forehand return, earned a break point to level in game four.
However, the Pennetta backhand put paid to that and the Briton would not get another chance.
Pennetta was increasingly dominant behind her first serve and, despite making her work, Keothavong could not keep the Italian at bay.
A second break of serve followed in game seven and Pennetta served it out with an ace that caught the line and barely bounced above knee height, prompting a grimace from Keothovang.
The Londoner gathered herself at the start of the second set and kept pace until game five, at which point a difficult task became all but impossible as Pennetta broke serve once again.
Keothavong could not win another game and was beaten soon after the hour mark, her first Grand Slam tournament since last Wimbledon coming to a swift end.
It was a marked improvement on last year, however, when she had the misfortune to draw world number one Dinara Safina in the first round and failed to win a game.
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