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Jordan Thompson is in to the US Open second round for the third time in four years but six other Australians all lost on day one at Flushing Meadows.

Opportunity knocks for Jordan Thompson after the Davis Cup star secured a spot in the US Open second round with a sapping four-set victory over Italy's Stefano Travaglia.

COVID-19 was the least of Thompson's concerns as he sweat out a 6-3 6-4 4-6 6-2 win in two hours and 42 minutes to be the only Australian to advance in sweltering New York heat on day one.

"It was very humid. It only took three or four games for my sweat to start dripping off my hat," he said.

"So if there was anything that was worrying, it was how much fluid I was losing.

"But, apart from that, I felt great; physically fine. I've been in a six-month training block, it feels like."

The 26-year-old's reward is an enticing one, a date on Thursday with lower-ranked Belarusian Egor Gerasimov, who upset 18th seed Dusan Lajovic in four sets.

Victory over the world No.72 would thrust Thompson into the last 32 for the first time at Flushing Meadows, having reached the second round in three of the past four years.

"Every match is an opportunity," he said.

Six other Australians were eliminated on Tuesday (AEST), including a total wipe-out of the women's contingent.

Ajla Tomljanovic's return to grand slam tennis ended in a gallant first-round loss to former world No.1 and 2016 US Open champion Angelique Kerber.

Leading the Australian women's charge in the absence of world No.1 Ashleigh Barty, Tomljanovic went down swinging in a 6-4 6-4 defeat to the tournament's 17th seed.

Tomljanovic struck 20 winners to Kerber's 15 but ultimately paid the price for 34 unforced errors in a see-sawing encounter at Louis Armstrong Stadium featuring eight service breaks.

Astra Sharma, Lizette Cabrera and Maddison Inglis battled hard for more than two hours before succumbing in three sets to more-fancied foes.

In a heartbreaker, Sharma suffered a 6-3 6-7 (5-7) 7-6 (7-2) near miss against Ukrainian young gun Dayana Yastremska, the 19th seed.

Cabrera lost 6-4 3-6 6-2 to Danka Kovinic of Montenegro, while Inglis went down 6-1 4-6 6-4 to Polish 24th seed Magda Linette in an admirable Flushing Meadows debut.

Arina Rodionova, who only earned an 11th-hour call-up after Lesia Tsurenko withdrew with an elbow injury on match day, lost 6-2 6-2 to American Madison Brengle.

Men's main-draw debutant Marc Polmans was unable to convert a two-sets-to-one lead in 6-4 6-7 (5-7) 3-6 6-4 6-2 defeat to US hope Marcos Giron.

HOW THE AUSSIES FARED ON DAY ONE OF THE US OPEN AT FLUSHING MEADOWS (PREFIX DENOTES SEEDING):

Men's singles, first round

Jordan Thompson bt Stefano Travaglia (ITA) 6-3 6-4 4-6 6-2

Marc Polmans lost to Marcos Giron (USA) - 6-4 6-7 (5-7) 3-6 6-4 6-2

Women's singles, first round

Ajla Tomljanovic lost to 17-Angelique Kerber (GER) 6-4 6-4

Astra Sharma lost to 19-Dayana Yastremska (UKR) 6-3 6-7 (5-7) 7-6 (7-2)

Maddison Inglis lost to 24-Magda Linette (POL) 6-1 4-6 6-4

Lizette Cabrera lost to Danka Kovinic (MNE) 6-4 3-6 6-2

Arina Rodionova lost to Madison Brengle (USA) 6-2 6-2