Kyrgios is aiming much higher than merely the fourth round, but the first-round elimination of world No.15 Roberto Bautista Agut has at the very least left the Wimbledon finalist with a seed-free path to the last 16.

Bautista Agut sent Kyrgios packing from New York last year in a straight-sets mauling.

But with the Spaniard out of the way, suddenly world No.50 Benjamin Bonzi, world No.71 Guillermo Gomez and world No.87 J J Wolf are the highest-ranked players standing between Kyrgios and a likely fourth-round showdown with top-seeded defending champion Daniil Medvedev.

Kyrgios took down Medvedev in Montreal this month but says he can't afford to look beyond his next match against Bonzi on Wednesday (Thursday AEST).

The Frenchman has cracked the top 50 this year for the first time after making four ATP quarter-finals, two semis and winning a pair of Challenger events.

"Very solid player," Kyrgios said. "He is having a great season."

Kyrgios, though, was again super impressive in ousting countryman Thanasi Kokkinakis in the first round in straight sets, leaving his doubles partner predicting another deep grand slam run for the 27-year-old.

"Nick's playing very confident right now, very free," Kokkinakis said.

"Obviously he always serves well and is probably playing with the most freedom I've ever seen from the back of the court. It puts a lot of pressure on your serve and groundies.

"If you don't serve as well as you need to, he's going to play. He's an incredible frontrunner. If he gets ahead, feels confident, it makes it really tough. Scoreboard pressure is everything."

Kyrgios headlines another all-star line-up of Australians on day three at Flushing Meadows.

Both Aussie No.1s - Alex de MInaur and Ajla Tomljanovic - also play second-round matches, as does Jordan Thompson following his stirring fightback from two sets down in his opener.

De Minaur, the 18th seed, squares off with Cristian Garin seeking redemption after blowing his own two-set lead in the Wimbledon fourth round against the clean-hitting Chilean.

Jordan Thompson takes on Colombian qualifier Daniel Elahl Galan, while Tomljanovic has a huge opportunity against returning Russian veteran Evgeniya Rodina.

Victory over the unranked Rodina - who is on the comeback from maternity leave - would thrust Tomljanovic into a third-round show-court duel with either retiring legend Serena Williams or world No.2 Anett Kontaveit on Friday.

AUSSIES IN ACTION ON DAY THREE OF THE US OPEN (prefix denotes seeding):

From 1am Thursday AEST

Men's singles, second round

18-Alex de Minaur v Cristian Garin (CHI), 1am

23-Nick Kyrgios v Benjamin Bonzi (FRA), about 5am

Jordan Thompson v Daniel Elahl Galan (COL), about 7am

Women's singles, second round

Ajla Tomljanovic v Evgeniya Rodina (RUS), about 8am

Australian Associated Press