The world number two turned on a master class of power and precision as he brushed aside Croatia's Ivan Dodig 6-4 6-3 6-3 to lead a trio of Spanish men into the fourth round.
French Open runner-up David Ferrer also moved through, beating Mikhail Kukushkin 6-4 6-3 4-6 6-4, while a third Spaniard, Tommy Robredo, ended the Cinderella run of British qualifier Dan Evans, winning 7-6 (6) 6-1 4-6 7-5.
Former world number one Caroline Wozniacki and the 2011 Wimbledon champion Petra Kvitova were among the high-profile casualties in a women's draw packed with surprises.
Four of the eight women already through to the fourth round are unseeded and three of the eight are Italian.
Camila Giorgi, who had to come through the qualifiers to reach the main draw, sent Wozniacki packing with a 4-6 6-4 6-3 win on Arthur Ashe Stadium while Flavia Pennetta knocked out the former U.S. Open champion Svetlana Kuznetsova 7-5 6-1. Roberta Vinci also won for Italy.
Nadal has been in great form in the past month, winning warm-up tournaments in Montreal and Cincinnati. He has not dropped a single set in getting to the last 16 at Flushing Meadows and believes he is still improving.
"I played better today than in the previous matches. (That's) always a positive thing," he said.
FEDERER LOOMING
Nadal's next opponent is Germany's Philipp Kohlschreiber, who beat towering American John Isner 6-4 3-6 7-5 7-6 (5), with Roger Federer looming as a possible quarter-final opponent.
While Nadal cruised into the next round and most of the men's results went as expected, a feisty Victoria Azarenka dropped her first set of the tournament before recovering to book her place in the last 16 of the women's draw.
A finalist last year and one of the favourites to win the title this season, the world number two and reigning Australian Open champion overcame a shaky start to beat Alize Cornet of France 6-7(2) 6-3 6-2.
The Belarussian was given a tough workout from Cornet and allowed her frustrations to boil over when the umpire ordered a point she had won be replayed.
"That was the most ridiculous thing there is," Azarenka said.
Former world number one Ana Ivanovic had to dig deep to avoid joining the exit queue. The Serbian was on the brink of defeat in her match against American Christina McHale before recovering to win 4-6 7-5 6-4. She plays Azarenka next.
"I know what to expect," said Ivanovic. "I really want to play against the best and challenge myself, because I'm ready to take them on."
BEATEN CHAMPIONS
Kvitova, the 2011 Wimbledon champion and seventh seed at Flushing Meadows, fell 6-3 6-0 to American wildcard Alison Riske.
The U.S. Open is the only grand slam where Kvitova has failed to at least make the quarter-finals and the Czech said she was unable to play near her best after contracting a virus.
"Unfortunately I was lying in the bed yesterday and I had a fever," Kvitova said. "I tried to play, tried to fight. But my body wouldn't let me fight."
Riske burst into tears after her win. The 23-year-old, who still travels with a security blanket that was given to her on the day she was born, has had a long road to her first fourth round appearance at a grand slam.
She first tried to qualify for the U.S. Open in 2007 and had never won a main draw match until this year. Now she is through to the last 16, and facing a showdown with Daniela Hantuchova, who saved four match points in her 3-6 7-5 7-6 (4) win over Israeli qualifier Julia Glushko.
"The blankie story is out," Riske said. "I'm used to it now. I can't deny it now. It's getting smaller by the week. It can fit in the palm of my hand."
(Editing by Nick Mulvenney)
