The American world number one joined Chris Evert and Martina Navratilova on 18 slams after a 6-3 6-3 victory at Flushing Meadows.
It marked Williams' third straight US Open crown and sixth in total, while it was her first in 2014.
At 32 and in form, she appears capable of edging closer to 22-time grand slam winner Steffi Graf and Margaret Court (24) before she retires.
Williams was in complete control in Sunday's decider in New York against her good friend Wozniacki, finishing with 29 winners and 23 unforced errors.
She dictated the encounter, highlighted by 2009 runner-up Wozniacki's paltry tally of four winners.
A pair of double faults and a Williams forehand winner led to the first break of serve in the second game.
Williams served at just 41 per cent in the first set, almost the only area of her game which was letting her down.
Wozniacki had pushed Williams to three sets twice this year and the Dane was in form leading into the final grand slam of the year.
But the 24-year-old 10th seed was pushed back by Williams' power, hitting just one winner for the set.
Williams' 15th of the set – a backhand down the line – saw her take it 6-3.
A break in the opening game of the second set put Williams in complete control as the match continued in a similar fashion.
Wozniacki, whose aggression had helped her reach the final, was forced into being ultra defensive.
As Williams' serve improved, she grabbed the only other break of the set in the ninth and final game.
Wozniacki sent a backhand long to see Williams claim her 18th grand slam title on her first championship point.