Maiken Caspersen Falla of Norway, who won the event in Sochi four years ago, took the silver medal and Yulia Belorukova, representing the Olympic Athletes of Russia, claimed the bronze.
Strong winds again whipped up the snow on the course as the field was whittled down from 68 starters to the six who contested the final.
The 24-year-old Nilsson, who has a superb sprinting pedigree, took control early in each of her races and the final was no different as she sped away up the first hill.
The sprint around the 1,176-metre course requires maximum effort and leaves no margin for error, but Nilsson barely had to look over her shoulder as she glided across the line, arms aloft, to claim victory just over three seconds ahead of Falla.
The Norwegian was locked in a furious battle for second with the 24-year-old Belorukova, and she had to call on every ounce of her experience to hold off the challenge of the Russian in a sprint finish, sliding a ski over the line to claim the silver.
With Charlotte Kalla winning the skiathlon, Nilsson's gold was the second for Sweden's women in Pyeongchang.
"I had a really good day, felt strong already in the prologue, I felt strong in quarters, and in semi I felt like I had some energy saved for the final," Nilsson told a news conference.
"I wanted to cross the finish line totally tired, so I just went for it in the last uphill."
Sochi champion Falla said she struggled in the conditions.
"The course I think it was hard, especially on the downhill, a little bit different form the last day. It was very difficult to ski down," she told reporters.
"The whole race, I think there as a lot of wind and cold temperatures. Not the easiest conditions, but it was nearly the same for everybody."
(Reporting by Philip O'Connor, editing by Ed Osmond)
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