Ivanovic became the first No. 1 seed to lose in the second round of a grand slam event since Justine Henin was upset at the French Open four years ago. No top-seeded woman's player had ever lost this early in the U.S. Open.
The earliest prior exit for a No. 1 seed had been a loss by Billie Jean King in the third round in 1973.
Coin, 25, is ranked 188th in the world. Not only is this her first grand slam tournament, it is her first event on the WTA Tour. She ousted Ivanovic 6-3, 4-6, 6-3 -- capitalizing on her third match point.
Ivanovic, the current French Open champion, has played in three grand slam finals. Coin will next meet Amelie Mauresmo.
Two-time champion Venus Williams breezed into the third round with a 6-0, 6-3 win over Rossana De Los Rios and Olympic silver medalist Dinara Safina was a 6-4, 6-3 winner over Roberta Vinci. Safina has reached the title match in six of her last seven tournaments.
Other winners in the women's draw included Timea Bacsinszky, Agnieszka Radwanska, Flavia Pennetta, Tathiana Garbin, Alize Cornet and Severine Bremond.