The three-time Miami Open champion will face Sweden's Rebecca Peterson in the second round.
Venus Williams upset Petra Kvitova in three sets while Osaka beat Mladenovic in straight sets.
The unseeded 38-year-old American came back strongly to beat Alize Cornet of France 6-3, 4-6, 6-0, setting up a meeting with top seed Simona Halep.
Venus Williams, who has reached the final at Melbourne Park twice, most recently in 2017 when she lost to sister Serena.
Terms of the agreement between Williams and the estate of Jerome Barson, 78, weren't included in the documents.
Five-time champ Venus Williams became the latest star to crash out in a 6-2, 6-7 (5/7), 8-6 defeat against Kiki Bertens.
The seven-time Grand Slam champion has now lost both her matches at major tournaments this year, having reached the Australian Open and Wimbledon finals in 2017.
Pliskova launched her bid for a season-ending triumph at the WTA Finals with a convincing 6-2, 6-2 victory over Venus.
Now Stephens and Keys, a pair of pals in their early 20s, will meet in the first Grand Slam title match for each, and the first all-American women's final at Flushing Meadows since 2002.
Anastasija Sevastova rallied to eliminate the five-time Grand Slam champion Maria Sharapova at Arthur Ashe Stadium.