Serena Williams began her bid to make history at the US Open in bizarre fashion as her opponent Vitalia Diatchenko retired after 30 minutes.
The world number one dropped just five points against a clearly injured opponent at Flushing Meadows.
Williams, 33, is hoping to complete the first tennis calendar Grand Slam in 27 years.
Men's top seed Novak Djokovic made swift progress, but fourth seed Kei Nishikori was beaten.
The Japanese player, last year's runner-up, went down 6-4 3-6 4-6 7-6 (8-6) 6-4 to Frenchman Benoit Paire.
"It's always very sad to lose in the first round, but I think he was playing good tennis so I don't think I played bad," said Nishikori.
Djokovic swept past Brazil's Joao Souza 6-1 6-1 6-1 to reach round two, but there were a host of upsets in the women's draw.
Ivanovic, the seventh seed, was beaten 6-3 3-6 6-3 by Dominika Ciblukova of Slovakia, and she was followed out of the tournament by five more seeds.
Draw opens up for Serena
Serena Williams was generous in her praise for Diatchenko after a workout that last just 37 points, with the American winning 32.
"I told her I was proud of her for coming out and making this effort, knowing she was injured," said Williams. "That's a great effort."
Her chances of reaching the women's final were boosted even before the world number began her title defence as seeds tumbled to leave the American with no other top-10 player in her half of the draw.
As well as Ivanovic, eighth seed Karolina Pliskova - who lost 6-2 6-1 to Anna Tatishvili - and 10th seed Carla Suarez Navarro failed to progress, while Maria Sharapova withdrew on the eve of the tournamentbecause of injury.
Former champion Svetlana Kuznetsova, seeded 30th, and former finalistJelena Jankovic, seeded 21st, also exited on day one.
Williams' sister Venus, the two-time champion, did advance to the second round, beating Monica Puig - only her second victory since losing in the last 16 at Wimbledon.
The last time Pam Shriver was seen on a singles court at the US Open was in 1996, but the American caused quite a stir when she returned to the field of play - microphone in hand.
Shriver sat down next to Coco Vandeweghe and proceeded to interview the American after she had taken the first set off Sloane Stephens on Louis Armstrong Stadium. The tennis world was quick to react...