The American, ranked one in the world, won 6-3 6-3 at Flushing Meadows in New York.
The Men’s final was won by World Number 16 and Marin Cilic, making him the first Grand Slam winner of his ranking in 10 years. The 25-year old Croatian beat Kei Nishikori 6-3 6-3 6-3.
Serena’s victory moves her to joint-fourth in the all-time list of major winners, alongside compatriots Martina Navratilova and Chris Evert.
Williams, 32, has now won three successive titles at the US Open, the scene of her first Grand Slam triumph 15 years ago.
“It was a really wonderful feeling,” said Williams, who was joined by Navratilova and Evert for the trophy presentation, when she also collected US$4m in prize money.
“I couldn’t have finished things in a better way. It is a pleasure for me to win here, I am really emotional. I couldn’t ask to do it at a better place.”
Wozniacki, a close friend of Williams, said: “Congratulations to Serena. She really deserved it today and played better than me.
Navratilova and Evert presented Williams with a gold bracelet to mark her
“She is an inspiration to me on and off the court and an unbelievable friend – and you definitely owe drinks later!”
Williams arrived in New York having failed to make it past the fourth round of a Grand Slam in 2014, but the American looked a class apart throughout the two weeks at Flushing Meadows.
Her dominance was such that she won the title without dropping a set, or more than three games in a single set.
The case for Wozniacki heading into the final centred around the Dane’s improved form this summer, which saw her push Williams to three sets twice before reaching her first Grand Slam final for five years.
“It was a final that won’t live live long in the memory, but an achievement that will. Serena Williams has finally drawn level with Evert and Navratilova in the record books, and has a Grand Slam winning span which now stretches over fifteen years.
“Wozniacki has had a great summer, but the aggressive front foot tennis which served her so well, was absent here, as Williams completed her seventh straight sets victory of the fortnight. It’s been a troubled year by her standards, but one which will end with her dominant position at the top of the world in tact.”
Wozniacki needed a strong start, however, and two double faults in her opening service game did not bode well.
The 10th seed was fortunate that Williams was also struggling in the early stages, the American thumping a second serve well long to drop serve for the second time in game five.
But it was Williams who came out on top of five consecutive breaks before finally holding for a 5-2 lead, and converting her second set point after 40 minutes.
Wozniacki’s athletic defensive skills had not been enough to win a set in which Williams was making just 41% of first serves and, sure enough, the American stepped up her game in the second.
Top women’s Grand Slam singles titles winners
Williams broke straight away, albeit thanks in part to a cruel net cord, and went close to moving 3-0 in front after a fabulous forehand winner.
It took 61 minutes for Wozniacki to hit her second winner of the match, a second ace, and she simply did not have the firepower to trouble the world number one.
A breathless 26-shot rally finally gave the 22,000 spectators a contest to engage with, but it took Williams to within two points of victory and there was no way back for Wozniacki.
Williams thumped her 29th winner of the afternoon to earn match point, and fell back onto the court in celebration when Wozniacki sent the ball long over the baseline.