Sharapova, seeded seven and the 2012 champion, needed just over an hour to beat fellow Russian, Ksenia Pervak, the world's 156th-ranked player, 6-1, 6-2.
The 27-year-old, who lost last year's final to Serena Williams, looked comfortable under the cloudy conditions on the Philippe Chatrier court, breaking her opponent five times.
Sharapova will next face Bulgaria's 2010 Wimbledon semi-finalist Tsvetana Pironkova.
"First matches at Grand Slams are always tough, no matter how prepared you are, no matter how many matches you've played," said Sharapova, now 13-1 on clay in 2014 with titles in Stuttgart and Madrid.
Japanese ninth seed Nishikori was left feeling as misrable as the Paris weather as he crashed out in the first round, clearly still suffering from his recent back injury.
Nishikori, 24, and coached by 1989 champion Michael Chang, was the first Japanese man in 75 years to make the fourth round in Paris in 2013.
But on Monday, there was never any sign that he would repeat that feat as he went down 7-6 (7/4), 6-1, 6-2 to Slovakia's Martin Klizan.
The world number 10 looked distinctly half-fit on Court 1 where he was broken 10 times, hit 10 double faults and committed 40 unforced errors
Left-handed Klizan, 24, one of six former junior champions in the main draw, goes on to face Robin Haase of the Netherlands.
After rain delayed the start of Monday's programme by more than an hour, play was halted again barely two hours later at 1230GMT when the heavens reopened.
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