British number one Kyle Edmund hopes to join compatriots Johanna Konta and Dan Evans in the second round of the US Open when he takes on Spaniard Pablo Andujar on Tuesday.
The 30th seed reached the fourth round in 2016 but lost to Italian Paolo Lorenzi in round one last year.
Edmund, 24, has won three of his last six tour matches since being knocked out in the second round at Wimbledon.
Konta beat Daria Kasatkina, while Evans overcame Adrian Mannarino on Monday.
- How the Britons did on opening day
- Williams thrashes Sharapova to advance
- Federer survives scare to progress
Elsewhere, 18-time Grand Slam champion Rafael Nadal kicks off the evening session on Arthur Ashe, taking on Australian world number 60 John Millman, who shocked Roger Federer in the fourth round last year.
Greek eighth seed Stefanos Tsitsipas, who suffered a shock first-round exit at Wimbledon, opens the proceedings on Louis Armstrong against Russian 21-year-old Andrey Rublev.
Australian 28th seed Nick Kyrgios was knocked out by Federer in the third round last year and he takes on 29-year-old American Steve Johnson, who has reached the second round on his last three appearances in New York.
- Live scores, schedule and results
- Alerts: Get tennis news sent to your phone
Also in action in the women’s draw is world number one and defending champion Naomi Osaka, who picked up her maiden Grand Slam last September in a dramatic victory over Serena Williams.
She followed it up with an Australian Open victory but has struggled since with injury and poor form, which Russian 20-year-old Anna Blinkova, ranked 84th, will hope to capitalise on.
Wimbledon champion Simona Halep gets her campaign under way on Louis Armstrong against American Nicole Gibbs, ranked 135th, while Czech sixth seed Petra Kvitova is up against compatriot Denisa Allertova on court 17.
American 11th seed and 2017 champion Sloane Stephens takes on Russian Anna Kalinskaya, ranked 127th, while Belarusian ninth seed Aryna Sabalenka is up against compatriot and two-time Grand Slam champion Victoria Azarenka.
And Wimbledon’s 15-year-old superstar Coco Gauff goes in front of a home crowd at her first US Open against Russian teenager Anastasia Potapova.