The 18-year-old Canadian trailed Ko by two shots heading into the final round but a six-under-par round of 65 pulled her into contention and she then kept her nerve as they replayed the 18th hole to land the tournament at Sahalee Country Club.
Henderson had birdies on the second and sixth holes but really put the pressure on when she sunk a putt from long range off the front of the green on the par-five 11th for eagle to reduce Ko’s lead to just one shot.
And further birdies on the par-three 13th and 17th hauled her level on six under par after Ko had sunk a birdie of her own at the 11th.
Both found the fairway off the tee at the extra hole and Ko then hit her approach to within 20 feet but Henderson sent her’s to three feet for a birdie to become the youngest winner in the event’s history.
“Yeah that’s amazing, as well, to think about all of the incredible players that have come before me,” Henderson told reporters. “And even I was reading some of the names on this trophy and it’s very, very cool.
“When that putt went in on number 11 for eagle, that was kind of like the huge jump forward, huge momentum changer. And then things just went pretty well. A good save on 14 out of the bunker. And then good putts on 17 and 18 to kind of finish it.”
Ariya Jutanygarn claimed third place on five under after a last-round five-under 66, while Anna Nordqvist of Sweden was the top European on level par and a tie for eighth.
Catriona Matthew finished joint-12th after closing with a 72 for a two-over-par aggregate. The excellent effort earned the 46-year-old Scot a $56,179 pay-day.