Novak Djokovic dropped a set in the first round of any Grand Slam tournament for the first time since 2010, but still managed to emerge with a 6-3 5-7 6-2 6-1 victory over Jerzy Janowicz of Poland at the US Open on Monday (Tuesday AEST).

The world No.1 had fitness issues during the match and there were plenty of signs of trouble, starting with a visit from a trainer who massaged Djokovic’s bothersome arm after only five games.

Asked about his health during an on-court interview, Djokovic deflected the question, saying: “I don’t think it’s necessary to talk about this now. I’m through. I’m taking it day by day.”

When the subject arose at his news conference, Djokovic again avoided addressing the topic, saying the trainer’s visit “was just prevention; it’s all good”.

During the match, Djokovic’s first and second serves were significantly slower than he usually manages. He flexed that right arm, the one he has used to wield a racket on the way to 12 Grand Slam titles, and appeared generally unhappy, covering his head with a white towel at changeovers.

Djokovic’s issues figure to loom large as the tournament progresses and were the most noteworthy development on the opening day at Flushing Meadows which did include drama elsewhere.

There was 20th-seeded John Isner’s comeback from two sets down to edge 18-year-old Frances Tiafoe before a rowdy, standing-room-only crowd at the new Grandstand. And 26th-seeded Jack Sock’s five-set victory over 18-year-old Taylor Fritz in another all-American match-up.

The match against Janowicz was Djokovic’s first match at a major since losing to Sam Querrey in the third round of Wimbledon, which ended the Serbian’s bid for a calendar-year Grand Slam after titles at the Australian Open and French Open.

Rafael Nadal cruised into the second round over Denis Istomin. Photo: AP

He exited the Rio Olympics in the first round this month, then sat out the Cincinnati Masters because of a sore left wrist.

“After all I’ve been through in last couple of weeks, it’s pleasing, of course, to finish the match and win it,” said Djokovic, who next plays Jiri Vesely, who he lost to at Monte Carlo in April. “Look, each day presents us some kind of challenges that we need to overcome, accept and overcome.”

Earlier in Arthur Ashe Stadium, Rafael Nadal stood near the net after winning his first Grand Slam match in three months – 6-1 6-4 6-2 against Denis Istomin – and unravelled the thick wrap of white tape protecting his all-important left wrist. He said he’s still not back to hitting his forehand the way he does when he’s at his best.

The good news for Nadal, he said afterward, is that the pain is gone from his wrist, which whips those violent, topspin-heavy forehands that are the key to his success.

Keys prevails in latest US Open finish

In the women’s draw, eighth-seeded Madison Keys was forced to stay up late before overcoming fellow American Alison Riske to close out Monday’s (Tuesday AEST) play at Arthur Ashe Stadium.

Keys, who reached the Australian Open semi-finals and Wimbledon quarter-finals last year, reined in her sometimes over exuberant groundstrokes to claim a 4-6 7-6(5) 6-2 win over the 60th-ranked Riske in a gruelling two hour, 25 minute slugfest.

With the night program delayed by more than an hour following a ceremony to mark the opening of the tournament, the final match ended at 1:48 am, making it the latest women’s match ever at the US Open.

“I just looked up and it’s almost 2 (am),” the 21-year-old Keys laughed in a post-match interview. “Who wants to go party?”

Madison Keys reacts after defeating Alison Riske in the first round of the US Open. Photo: AP

Next up for Keys, who twice received treatment on her right shoulder, is another American, 16-year-old Kayla Day, the US national junior champion and youngest player in the draw.

Earlier on day one, Rio 2016 Olympic Games gold medallist Monica Puig lost her first round match 6-4 6-2 against 61st-ranked Zheng Saisai.

Australian Open winner Angelique Kerber maintained steady course as she tries to displace Serena Williams from the top women’s ranking, with the No.2 seed rolling into the second round as her opponent quit after seven games.

The German was untouchable against Polona Hercog, who went down in a heap 6-0 1-0.

The 2015 finalist Roberta Vinci, the seventh seed who shocked Williams in a semi-final a year ago in New York, started with a defeat of German Anna-Lena Friedsam 6-2 6-4.

Former world No.1 Caroline Wozniacki began trying to correct an injury-plagued season of poor form, beating US player Taylor Townsend 4-6 6-3 6-4.

Third seed Garbine Muguruza almost fell victim to the heat but held on to beat Elise Mertens of Belgium 2-6, 6-0, 6-3.