The second seed has looked in fine form at Flushing Meadows and he needed only an hour and 37 minutes to defeat Frenchman Julien Benneteau 6-3 6-2 6-2.
Benneteau is the 31st seed and the man who almost beat Roger Federer at Wimbledon this year but he could do nothing to threaten Djokovic.
The Serb, who beat Rafael Nadal in the final last year, had been slightly off colour after losing to the Spaniard in the French Open final to see his hopes of four straight grand slam titles go up in smoke.
But he has hit form again on the north American hard courts, winning the title in Toronto and reaching the final in Cincinnati, and he made it only 14 games dropped in three rounds.
Benneteau simply could not live with Djokovic’s power and precision from the back of the court and time and again found himself out-rallied as the Serb powered away 41 winners and made only 12 unforced errors.
Djokovic is not used to playing in the first match of the day, but there was certainly no lack of sharpness from the world number two.
He said: “He’s a quality player and has a lot of variety in his game, so I came to the match knowing that I have to start very strong.
“And winning the first set obviously brought me a lot of momentum and confidence to continue on playing well. I felt from the start that from the baseline I was very comfortable, both defence and offence, in that position.
“So I tried to be aggressive and not allow him to come to the net because he plays good when he’s in control.”
Ferrer and Hewitt are possibly the game’s two grittiest competitors and it was no surprise the match lasted for more than three hours.
Hewitt, the 2001 champion, needed a wild card to get into the tournament as he is still working his way back from foot surgery earlier this year but there are signs that he is rediscovering some of his old form.
The 31-year-old had five set points in the first set tie-break but Ferrer simply would not give in, setting up the set point he took with some incredible retrieving.
Hewitt levelled but went an early break down in the third set and the five-setter he had against Gilles Muller in the previous round began to catch up with him as Ferrer rather ran away with it in the fourth to win 7-6 (11/9) 4-6 6-3 6-0.
Ferrer said: “Maybe the first set was the key. When I won the first set, after almost one hour and a half, it was very tough.
“He won the second set but I think he was more tired than me. So in the third and in the fourth I played with more power. I changed my forehand and in the fourth he was really tired.”
Seventh seed Juan Martin Del Potro made it through in straight sets against fellow Argentinian Leonardo Mayer, taking his sixth match point to win 6-3 7-5 7-6 (11/9).
The 2009 champion had been a break down in the second set, while he also needed treatment for a knee problem, and he let out a huge roar when Mayer hit the final return long.
In the fourth round, Del Potro will face Andy Roddick, who again delayed his retirement for another day as he defeated talented Italian Fabio Fognini 7-5 7-6 (7/1) 4-6 6-4.
Roddick was playing his 50th match on Arthur Ashe Stadium, more than any other player except Roger Federer, and he eventually overpowered Fognini.
Roddick announced earlier this week that he will retire after the tournament and he was cheered to the rafters by the crowd on tennis’ biggest stage.
Meanwhile, at almost the same time as Roddick was clinching an emotional victory, Stanislas Wawrinka eased past an error prone Alexandr Dolgopolov 6-4 6-4 6-2 to set up an intriguing fourth-round clash with Djokovic.