Last year's beaten finalist showed no signs of weakness in running out a convincing 6-0 6-0 winner in just an hour and book her place in the second round where she will come up against her compatriot Vitalia Diatchenko.
The 23-year-old Russian was simply too strong for her Britain's brightest hope in the tournament, who is ranked 48th in the world, producing an aggressive and near flawless performance.
Keothavong was completely outclassed, and could only muster a break point in the first game and then once again half way though the opening set. The British number one might have taken a game in set two, but at 40-0 up she served two double faults and eventually conceded to go 6-0 6-4 behind.
Safina has already claimed victory on clay twice this year, in Rome and Madrid, and is favoured to take the French title this time around.
Her second-round opponent, Diatchenko, defeated home girl Mathilde Johansson in her opening match on Sunday in a far from clear-cut victory as she had to come from a set down to win the contest 2-6 6-2 10-8.
Meanwhile, defending French Open champion Ana Ivanovic got through her opening round with relative ease, beating Italy's Sara Errani 7-6 (7-3) 6-3. The Serbian needed 72 minutes to take the first set though and produced only flashes of the form that saw her take the world number one ranking last season.
Inconsistent serving ensured she was forced to work for her place in the second round, but she took the opening set in a tiebreaker as Errani made a series of costly mistakes.
Ivanovic looked more comfortable in the second set and controlled much of the play. It was her superior forehand technique that proved to be the key and she sealed victory with a powerful bullet at the death.
The 21-year-old will meet Thailand's Tamarine Tanasugam in the second round following the 32-year-old's 6-3 5-7 7-5 win over France's Camille Pin on Monday.
There were opening-round victories also for ninth seed Victoria Azarenka (Bulgaria), 11th seed Nadia Petrova (Russia) and 15th seed Jie Zheng (China).
There was an unexpected defeat for 16th seed Amelie Mauresmo of France, who fell in straight sets to Germany's Anna-Lena Greonefeld, 6-4 6-3.
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