Angelique Kerber needed just over 30 minutes to get her pursuit of a first US Open off to a winning start Monday as Novak Djokovic and Rafael Nadal prepared to make their bow.

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

Kerber, who next faces either Alize Cornet of France or Mirjana Lucic-Baroni of Croatia, insisted she will not be distracted by possibly dethroning Serena Williams as world number one by the end of the tournament.

Three seeded players lost early on the opening day with French 13th seed Richard Gasquet, a semi-finalist three years ago, the biggest casualty.

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

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

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 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, defending champion Djokovic and fellow two-time winner Nadal start their campaigns but with both men under injury clouds.

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

Nadal is also battling the effects of a left wrist problem which forced a mid-tournament withdrawal from the French Open and sidelined him until the Olympics where he was a gold medal winner in the men's doubles.

The injury concerns, combined with the absence for the first time since 1999 of five-time winner Roger Federer, have put 2012 champion Andy Murray in the position of favourite.

Djokovic starts his bid for a third major of 2016, and 13th of his career, against Polish giant Jerzy Janowicz, who was a Wimbledon semi-finalist in 2013.

A serious knee injury has limited Janowicz to just six matches all year and seen his world ranking collapse to 228.

Nadal, the 2010 and 2013 champion in New York, tackles Denis Istomin of Uzbekistan.

The Spaniard has a 4-0 career record over world number 107 Istomin, including a win over the Russian-born player at the 2010 US Open.

It will be a difficult task for the injured Nadal to come back from here.

Nadal closes the daytime session on Ashe while Djokovic starts the evening entertainment.

In between, the tournament will stage its opening ceremony with British singer-songwriter Phil Collins making his first concert appearance in six years.