The victory gave the world number one the 16th Grand Slam title. Only his longtime rival Roger Federer has more, with 19.
Besides his triumph in New York, Nadal also won the French Open in June and has collected two major titles in the same year for the first time since 2013, when he won the last of his two US Open crowns.
Federer won the season's other two Slam trophies at the Australian Open, beating Nadal in the final, and Wimbledon, illustrating the two Grand Slam greats' enduring power.
World number 32 Anderson was the lowest-ranked US Open men's finalist since the ATP rankings began 44 years ago. He had never before been past the quarterfinals at any major tournament in 33 tries.
The final was a lopsided one where Nadal was never really tested by his opponent. He converted four of his nine breaking points while Anderson never had breaking chances. Anderson powered 10 aces compared to one from Nadal, but he made 40 unforced errors to just 11 from Nadal.
Nadal said: "It's unbelievable what happened this year. After a couple of years with a lot of trouble and pain, I've been playing a very high level in the sport."
"To close the Grand Slam year winning at New York feels good, that's one of the events that's really full of high energy. The US Open feels a little bit like home," said Nadal, who has yet to lose to Anderson, now standing 5-0 in the series.
Anderson, 31, gave all thumbs up to Nadal, saying "I know we're the same age but I feel like I've been watching you my whole life".
"He's one of the toughest competitors in the game and one of the greatest ambassadors of our sport," he added.