Nadal, just hours after rival Roger Federer was taken to five gripping sets by France's Gilles Simon, was made to sweat only by the hot sun on Rod Laver Arena as he dispatched America's Sweeting 6-2, 6-1, 6-1.
The Spanish world number one said he was now fully recovered from a virus which struck him in Qatar as he bids to hold all four major titles for the first time since 1969, a feat which would eclipse even the illustrious Federer.
"Every day I feel better and I am now totally recovered," he said.
Nadal, forced out injured last year as defending champion, is on a 23-match Grand Slam streak after last year winning the French Open, Wimbledon and his first US Open. He won his opener here 6-0, 5-0 when Maros Daniel retired hurt.
Belgium's Clijsters also dropped her first games of the tournament -- after a jaw-dropping 6-0, 6-0 whitewash of Dinara Safina in the first round -- as she easily dispatched Spaniard Carla Suarez Navarro 6-1, 6-3.
The US Open champion, who has an outside chance of regaining the top ranking here, said she was delighted with her form and was not contemplating last year's third-round disaster, when she suffered her heaviest Grand Slam defeat.
"I don't think I've ever played a match like that. So it was very easy in a way to also forget about it, as well," she said of the bewildering 6-0, 6-1 reverse to Nadia Petrova in 2010.
"If that would be something that would occur more often, it would be in my mind. I would feel like I had to do something about it."
China's Peng Shuai handed out the tournament's biggest shock when she downed former number one Jelena Jankovic 7-6 (7/3), 6-3 to equal her best Grand Slam performance. She will meet Japan's Ayumi Morita in the third round.
The 25-year-old missed much of last summer after suffering appendicitis and injury, but she won the Asian Games title in November and started 2011 in top form, reaching the semi-finals in Auckland and Hobart.
Meanwhile defending men's champion Federer cut a chastened figure after his late-night thriller, when Simon rallied from two sets down to put the all-time Grand Slam record-holder on the ropes.
The 16-time major-winner was perilously close to his worst Grand Slam performance since 2003 before getting the crucial break in the deciding set and acing his fifth match point.
"I was like, 'This can't be true, right?'," Federer said afterwards, when asked what was going through his mind. "I definitely felt something was not going my way," he added.