The 30-year-old was made to battle extremely hard by world number one Victoria Azarenka, who served for the match in the decider but could not hold off Williams as she triumphed 6-2 2-6 7-5.
Since losing in the first round of the French Open to Virginie Razzano, Williams has won 26 out of 27 matches, collecting a fifth Wimbledon title, two Olympic gold medals and now her fourth US Open, and she is not done yet.
The American said: "Even though I'm 30, I feel so young and I've never felt as fit and more excited and more hungry.
"Even with this win, I'm sitting here so excited to play the next grand slam and see what I can do, just to do more. I love that feeling. I feel like it's overdue. I'm excited I feel that way."
Williams sits in sixth place in the all-time list of grand slam singles winners, three titles behind Martina Navratilova and Chris Evert, seven adrift of Steffi Graf and nine behind Margaret Court.
Reflecting on her place in history, Williams said: "I haven't thought about that until recently. I never thought I would even come close to breaking those records.
"But if I can play consistently and play some more matches at Wimbledon, then it will be awesome. We'll see. If I could win two a year it would be great."
Williams certainly left a different impression at Flushing Meadows this year than in her previous two appearances in 2009 and 2011.
Both times she lost her temper, first with a lineswoman and then with umpire Eva Asderaki, earning fines and widespread criticism from inside and outside the sport.
Asked about it before the final, Williams had been quick to remark the tournament was not finished yet, and the crowd reacted when the American was penalised for a foot fault in the second set, which had been the source of her anger in 2009.
But, a hard stare at the line judge aside, Williams remained calm, and she said: "This is the first year in a long time I haven't lost my cool.
"I think everyone thought about last year. That's never on my mind, because I was just focused. I was just thinking: 'Okay, which foot was it?' So I would know not to do that again."
Williams won her first grand slam title at the US Open in 1999 when she was 17, and the 13-year span is the longest at any grand slam tournament in the Open era.
She added: "I just think that it's exciting to have this opportunity. And 13 years is a long time between the first and the last.
"I was reading yesterday [Sunday] how Pete Sampras won in 1990 and 2002. That was a 12-year span. That was pretty awesome. For me to get this, and I'm at number 15 now. It's so cool. I'm so excited."
Many people had expected Williams to romp to her 10th win in 11 meetings with Azarenka but the Belarusian showed she is no token world number one.
She began the season with a 26-match winning streak and this summer had her best results on grass, losing to Williams in another close match at Wimbledon and then winning the bronze medal at the Olympics.
Reflecting on her first US Open final, she said: "It's a great achievement, there is no doubt. It's difficult to sink everything in at this particular moment, because right now I feel sad.
"I feel proud of myself in one way, but still sad. But in a few days, when I go home, I'll be more than happy with the summer.
"I think I'm in pretty good shoes, sitting here as a finalist of the US Open for my first time."