The 21-year-old Poland won 6-2 7-6 (7-5) in one hour and 52 minutes at Flushing Meadows, New York to secure the season's final major trophy. She is already a two-time French Open champion.
Jabeur, 28, also lost in the Wimbledon final in July. The Tunisian was bidding to become the first woman from Africa to win a Grand Slam title.
Swiatek had won her nine previous finals without dropping a set. She will remain the world number one, with Jabeur moving up to a joint career-high WTA ranking of second.
"It's something that I wasn't expecting, for sure. It's also like a confirmation for me that the sky's the limit," said Swiatek, who is 55-7 in tour-level matches with seven trophies in 2022.
"I'm proud. Also surprised little bit," she added.
She also became the first woman since Angelique Kerber in 2016 to collect two major titles in a single season.
"She’s really set the bar very high. It’s great for our sport,” said Jabeur, who is the first African woman and first Arab woman to reach a Grand Slam final.