Australian Open champion Aryna Sabalenka has overcome a shaky start to reach the second round of the US Open as she chases a second grand slam title and the world No.1 ranking in New York.

Twice a US Open semi-finalist, second seed Sabalenka was nowhere near her best but showed composure when it mattered to overpower unseeded Belgian Maryna Zanevska 6-3 6-2 on Tuesday night.

The Belarussian was wobbly early, producing five double faults to drop serve twice, but Zanevska was unable to capitalise.

The 30-year-old Zanevska, who announced her intention to retire after the tournament due to a chronic back issue, broke for the early lead in the second set but Sabalenka clawed her way back to 2-2 and never looked back.

"First of all I want to thank you guys for staying because if I would be you, after the third double fault I'd leave the stadium," Sabalenka told the crowd.

"It was a tough start, it was so humid. I couldn't hold my racquet. I'm glad I was able to get through this situation and get this win." 

Sabalenka can claim the world No.1 ranking from Iga Swiatek if she emerges from the US Open with a better result than the Pole.

Third seed Jessica Pegula and former finalist Madison Keys punched their tickets into the second round with routine victories that bolstered hopes for a homegrown winner.

However, fellow American Venus Williams' 100th career US Open match produced her most lopsided loss at the slam where she won the trophy in 2000 and 2001.

Williams, at 43 the oldest player in the field, was eliminated 6-1 6-1 by Belgian qualifier Greet Minnen.

Pegula, whose US Open tune-up included a triumph in Montreal just over two weeks ago, earned a 6-2 6-2 victory over Italy's Camila Giorgi and 2017 runner-up Keys beat Dutchwoman Arantxa Rus 6-2 6-4.

An American woman has not won the US Open since Sloane Stephens beat compatriot Keys in the 2017 final but Pegula has shown she just may be hitting her stride at the perfect time.

"I think we are all hoping that we hit the right form going into a slam, especially if you get through the first week trying to hit that stride in the second week," Pegula said.

"But you never really know what's going to happen."

At Louis Armstrong Stadium, Keys went up a double break for an early 3-0 lead en route to sealing the opening set in 32 minutes and never looked back.

The first 21 times Williams entered the US Open, she went 21-0 in the first round. But Tuesday's loss was her third consecutive opening-round loss at Flushing Meadows.

"For me, it was incredible to play a legend like her. I have huge respect," said Minnen, who is ranked No.97. "To be there at 43 years old, it's amazing really."

Williams - whose younger sister, Serena, retired from tennis after last year's US Open - owns seven major championships, including five at Wimbledon.

But she has lost in the first or second round in each of her past 12 slam appearances.

The spectators seemed thrilled just to get a chance to see her play, sending her off with a standing ovation.

Tunisian fifth seed Ons Jabeur advanced after she overcame breathing difficulties to secure a gritty 7-5 7-6 (7-4) win over Colombia's Camila Osorio.

Also advancing was China's Yafan Wang who stunned French seventh seed Caroline Garcia 6-4 6-1.