Safina, who was beaten by the Frenchwoman in the Australian Open second round last month, took advantage of Mauresmo's weak serve to clinch her third WTA title in two hours and 19 minutes.
Second-seeded Mauresmo, a winner in Paris in 2001, has now lost three finals in the Pierre de Coubertin hall after two previous defeats by Serena Williams in 1999 and 2003.
"She took her chance. She was very solid. I had many chances in the first set, which I didn't convert," said Mauresmo. "Obviously, I didn't play my best tennis but she deserves her win."
Australian Open winner Marat Safin's younger sister Safina, hitting baseline winners, surprisingly won the first set in an hour after breaking Mauresmo's serve three times in a row.
However, the Frenchwoman took a 2-0 lead in the second set before ramming the advantage home as she broke Safina again in the fifth game, forcing the Russian to a decider.
Three forehand errors by Mauresmo gave Safina a 3-1 lead in the final set and the Russian then held serve before breaking an embittered Mauresmo again to serve for the match.
The Frenchwoman came back to 5-3 but eventually bowed out on Safina's first match point.
