Djokovic, who had won only two matches in the hard court run-up to the season's final Grand Slam after getting married just days after his Wimbledon triumph, was back to his best once the center court spotlight shone on him at Flushing Meadows.
The 2011 champion treated his first-round match against unseeded 22-year-old Argentine Diego Schwartzman like a breezy workout, dominating in all phases with 24 winners including seven aces in a 6-1, 6-2, 6-4 rout.
His fast work followed a scintillating finish by French Open champion and 2006 winner Sharapova, as the fifth seed won 10 straight games to prevail 6-4, 6-0 after falling 2-4 behind against her Russian compatriot and old friend Maria Kirilenko.
Despite the night programme starting one hour later than scheduled due to ceremonies featuring bands, speeches and fireworks, Djokovic enabled the New York night crowd to head to the exits shortly before the stroke of midnight.
"I'm very pleased," the Serbian world number one said in a courtside interview after his 97-minute win. "It's never easy to start a US Open smoothly."
Several of the favorites at Flushing Meadows could attest to his opinion.
Busy bees made life difficult for two grizzled veterans and a pair of favourites were forced to work overtime on a hot, steamy day at the US National Tennis Center that drew a combined 57,000 fans to the day and night sessions.
Eighth-seeded 2012 champion Andy Murray fought off cramps to beat Dutchman Robin Haase in four painful sets, while women's second seed Simona Halep lost an early tiebreak to US debutant Danielle Collins before claiming victory.
And in an intriguing match-up of 19th seed Venus Williams and Kimiko Date-Krumm of Japan, the oldest players in the women's draw, some pesky bees joined in and refused to leave them alone.
Major Cramping
Murray appeared on course for an easy victory before he fell victim to cramps that left him stretching and straining to get comfortable before clinching a 6-3, 7-6(6), 1-6, 7-5 victory over Haase.
"I felt extremely good before the match, and I did train very, very hard to get ready for the tournament," said Murray, one of the fittest players on the ATP Tour.
"My quads were cramping, then it started to get to my lats, then my forearms," he added. "I just tried to hang around and at the end I was trying to play without moving my legs much and managed to get through."
Murray said he might consult with a nutritionist before meeting his second-round opponent, Germany's Matthias Bachinger.
A less serious intrusion hit the irresistible women's clash between seven-times Grand Slam singles winner Williams and Japan's remarkable Date-Krumm, who were beset by bees.