The American clocked a time of just over two hours to finish top of the pile this season, with compatriot Sarah Groff taking second and New Zealander Andrew Hewitt rounding off the podium places.
Jorgensen showed remarkable poise to stick to her tactics despite losing ground on the leading pack on the 1500-metre swim and 43.2-kilometre cycling section.
It was the 28-year-old's brilliance on two feet that proved pivotal, her 10km run seeing her eclipse a 70-second deficit to claim the title that was won by Britain's Non Stanford last year.
In Stanford's absence, Jorgensen was left to revel in her glory after finishing ahead of Hewitt and Nicky Samuels on the day.
"I didn't execute too well on the swim and the first lap on the bike, but towards the end I was able to reel it in so I'm really happy," she said.
It was Jorgensen's fifth win of a superb season and one of her most hard-fought, with Hewitt having led alongside Carolina Routier, Margit Vanek and Rebecca Clark after the swim.
A larger group of front-runners increased their advantage over the chasing pack on every lap of a gruelling bike stage, but nobody could match Jorgensen across the final 10km.
Jorgensen did not need to win the event in order to take overall glory, but clearly had designs on a fairytale climax as she became the first American World Triathlon Series champion since Sheila Taormina in 2004.
Hewitt, meanwhile, has now claimed four podium finishes but the 32-year-old has never taken top honours.