The Wimbledon champion, playing his first match on Arthur Ashe Stadium since falling to Stan Wawrinka in the 2016 final, received a brutal welcome back as soaring temperatures and suffocating humidity prompted organizers to offer the men a 10-minute mid-match heat break for the first time ever.
"We both struggled. We were not the only ones today. Brutal conditions," said Djokovic, who called for trainers who enveloped him in ice packed towels late in the second set.
"I had to find a way to dig myself out of the trouble."
Until late in the third it was "survival mode" said Djokovic, who endured a rocky start to the season after elbow surgery before breaking through for a 13th Grand Slam title at Wimbledon.
His Cincinnati Masters victory over Roger Federer stamped him a US Open favorite along with defending champion Rafael Nadal, despite his modest sixth seeding.
Federer, the second seed, was to launch his quest for a sixth US Open title -- and a first since 2008 -- not under the blazing sun but under the floodlights on Ashe against Japan's Yoshihito Nishioka.
He headlined a night session that also featured 2017 women's runner-up Madison Keys taking on France's Pauline Parmentier on Ashe, while over on Armstrong, Maria Sharapova launched her latest bid to revive her Grand Slam career against Switzerland's Patty Schnyder, out of retirement and, at 39, the oldest player to qualify for a Grand Slam main draw.
Mercurial Australian Nick Kyrgios, the 30th seed, will be in action on Armstrong, taking on Moldova's Radu Albot with a possible third-round meeting with Federer in the offing.
Australian Open champion Caroline Wozniacki played in the heat of the day, but the weather oppressing so many seemed to suit the Dane as she defeated 2011 champion Samantha Stosur 6-3, 6-2.
"I just tried to cool down between games, used ice," said Wozniacki, who also imagined she was on the beach "margarita in hand".
While Wozniacki got by with the help of eight double faults from Stosur and "trying to think cool thoughts," for France's Alize Cornet the steamy conditions were a "nightmare".
Cornet wept as she sat courtside, telling doctors she felt ill amid her three-set loss to Johanna Larsson of Sweden.
With the women already taking advantage of a WTA recommended "heat break" prior to a third set, organizers decided Tuesday afternoon that the men would be afforded a similar 10-minute off court rest prior to a fourth set under an Extreme Heat Policy.
- 'Magnificent feeling' -
It wasn't enough to prevent half a dozen retirements, with Italy's Stefano Travaglia, Argentine Leonardo Mayer, Lithuanian Ricardas Berankis, Russian Mikhail Youzhny and Serbian Filip Krajinovic all victims of the heat and Romanian Marius Copil succumbing to an arm injury.
"I had heat stroke," Mayer said of his decision to call it quits. "I was not going to die on the court, tennis is not for that."
Djokovic called it "sad".
"There's so much cramping going on," he said, noting that while it's a player's responsibility to be fit "there are some conditions that are so extreme that as fit as you are you can't just not feel it."
Although he appreciated the heat break, he wasn't sure if organizers should go further and give up on the 25-second serve clock, newly introduced at the US Open to strictly monitor time players take between points.
"When a rule is implemented, it's kind of hard to just switch the shot clock off just because the conditions are difficult and brutal," Djokovic said.