NEW YORK - Defending champion Naomi Osaka starts off Wednesday's US Open schedule at Arthur Ashe Stadium with second seed Daniil Medvedev and third seed Stefanos Tsitsipas to follow in other feature matches.

Osaka seeking her fifth career Grand Slam title and third US Open crown in four years, plays a second-round match against 145th-ranked Serbian qualifier Olga Danilovic.

The 23-year-old Japanese third seed has never faced her 20-year-old rival.

Russian second seed Daniil Medvedev, the 2019 US Open and 2021 Australian Open runner-up, meets Germany's 57th-ranked Dominik Koepfer. Medvedev beat Koepfer in the fourth round of the 2019 US Open.

Sloane Stephens, the 2017 US Open champion, faces 17-year-old Coco Gauff in a first-time battle of Americans to open the night session on Ashe. Gauff is ranked 23rd, 43 spots ahead of Stephens.

The final match on Ashe sends world number three Tsitsipas of Greece against France's Adrian Mannarino.

Tsitsipas has become a focus of complaints for long and untimely toilet breaks, arousing the ire of three-time Grand Slam champion Andy Murray of Britain in his first-round victory and Olympic champion Alexander Zverev two weeks ago in Cincinnati.

Mannarino, ranked 44th, has split two meetings with Tsitsipas, both in 2019. Tsitsipas won at Madrid but was forced to retire after splitting sets in Zhuhai.

Spanish ninth seed Garbine Muguruza meets Germany's Andrea Petkovic in the first match Wednesday at Louis Armstrong Stadium with last year's US Open runner-up, 18th seed Victoria Azarenka of Belarus, up next against Italy's Jasmine Paolini.

South African Kevin Anderson meets Argentina's 11th-seeded Diego Schwartzman in the first Armstrong night match.

Launching matters on the Grandstand will be Russian fifth seed Andrey Rublev and Spaniard Pedro Martinez with Belarus second seed Aryna Sabalenka next against Slovenia's Tamara Zidansek.

AFP