Rafael Nadal and Angelique Kerber shrugged off sweltering temperatures to reach the US Open second round Monday as French Open champion Garbine Muguruza survived a worrying health scare.

Nadal, the 2010 and 2013 champion, took his perfect first round record in New York to 12-0 with a 6-1, 6-4, 6-2 win over Denis Istomin of Uzbekistan.

The Spaniard's reward for a fifth win in five meetings against the Russian-born player is a match-up with Italian veteran Andreas Seppi.

A wrist injury forced Nadal into an early retirement at the French Open and sidelined him from Wimbledon before a gold medal run in the doubles at the Olympics helped ease his misery.

"The most important thing is that I am here in New York. Injuries are part of the career. I had a hard time this year," said the fourth seed.

Kerber needed just over 30 minutes to get her pursuit of a first US Open title off to a winning start.

The second seed and Australian Open champion was leading Polona Hercog 6-0, 1-0 when the Slovenian called it quits, clearly wilting in the 33-degree heat, having won just nine points.

"It's not the way I wanted to win, but I am playing well and feeling good," said the German star.

Kerber, a semi-finalist in 2011, next faces Mirjana Lucic-Baroni of Croatia.

Spanish third seed Muguruza carved out a gritty 2-6, 6-0, 6-3 win over Belgian qualifier Elise Mertens, ranked at 137.

But the French Open champion needed courtside treatment from a doctor after dropping the first set on the Louis Armstrong Court.

Doctor's orders

The consultation certainly worked as she reeled off the next seven games to lay the foundation for her win.

Muguruza plays Anastasija Sevastova of Latvia for a place in the last 32.

French 13th seed Richard Gasquet, a semi-finalist three years ago, was the day's biggest casualty.

He went down to 6-2, 6-2, 6-3 to British world number 84 Kyle Edmund.

America's John Isner, seeded 20, almost joined Gasquet at the exit before coming back from two sets down to beat 18-year-old compatriot Frances Tiafoe.

Isner, who fired 35 aces, triumphed 3-6, 4-6, 7-6 (7/5), 6-3, 7-6 (7/3) after three and a half hours against the youngest player in the draw.

Croatian seventh seed Marin Cilic, the 2014 champion, eased past Brazil's Rogerio Dutra Silva 6-4, 7-5, 6-1.

Flamboyant French 10th seed Gael Monfils took his summer hardcourt record to 15-2 with a 6-4, 6-2, 7-6 win over Gilles Muller of Luxemburg.

Monfils almost suffered a freak accident when a giant courtside clock fell towards him as he collided with the back wall, chasing down a Muller shot.

"When you are in the moment you don't feel really anything. Just jump. I saw a wall, but it was quite lucky," admitted Monfils.

Svetlana Kuznetsova, the 2004 champion, needed only 58 minutes to beat old rival Francesca Schiavone 6-1, 6-2.

The pair famously played the longest women's match of all time at the 2011 Australian Open where Schiavone saved six match points in a four hour 44-minute marathon.

Double Wimbledon champion Petra Kvitova beat Jelena Ostapenko 7-5, 6-3 while former world number one and two-time US Open runner-up Caroline Wozniacki downed US qualifier Taylor Townsend 4-6, 6-3, 6-4.

The Flushing Meadows complex was showcasing its gleaming $600 million refit which includes a retractable roof over Arthur Ashe and a brand new Grandstand court.

However, the old Grandstand court, due to be demolished after the tournament, was pressed into action after Court 10 was deemed unplayable.

Later Monday, world number one and defending champion Novak Djokovic, whose last major ended in a shock third round exit at Wimbledon, starts against Jerzy Janowicz of Poland.

Djokovic, the 2011 and 2015 champion, admits he is "not 100 percent" after suffering a wrist injury on the eve of the Olympics where he was a first-round loser.

Women's top seed Serena Williams and 2012 champion Andy Murray will get underway on Tuesday.

Williams is chasing a record seventh US Open and will equal Steffi Graf's record of 186 successive weeks at world number one.