A commanding six strokes ahead of the chasing pack overnight, Choi triple-bogeyed the 10th and did well to salvage pars at the 12th and 13th before regaining momentum to close with a one-over-par 73 at Blackwolf Run.
The 24-year-old birdied the 15th and 16th in dazzling sunshine and shrugged off a bogey at the last for a seven-under total of 281, finishing four ahead of her fellow Korean and playing partner Amy Yang (71).
World number five Choi embraced her caddie in delight before being showered in champagne by her compatriots after becoming the sixth Korean to win the US Women's Open, and the fifth in the last eight years.
After being presented with the champion's medal and the glittering US Women's Open trophy, Choi was asked greenside how she had recovered from her triple-bogey at the 10th.
"I tried to forget it from there," she replied with a smile. "And then I had a really good (birdie) bounceback on 11.
"I also had a really good save for par on 12 so I got some momentum from 11 and 12 and that's how I kept it going until the 18th hole."
With her US Women's Open triumph, Choi emulated fellow Koreans Pak Se-Ri (at Blackwolf Run in 1998), Birdie Kim (2005), Park In-Bee (2008), Ji Eun-Hee (2009) and Ryu So-Yeon (2011).
"Actually before Se-ri won in 1998, my dream was just being a professional golfer," said Choi, who is projected to climb to second in the world rankings on Monday.
"But after I watched her (win), she really inspired me to be a LPGA player. So I really appreciate what Se-Ri did before and she is a legend in Korea."
Five-times Major champion Pak, whose victory here 14 years ago sparked the Korean surge at the highest level in women's golf, led the charge on to the 18th green to congratulate Choi with champagne bottle in hand.
"She said, 'Hey, Na-Yeon, I'm really proud of you. You did a really good job.' She talked to me a lot, and she was hugging me," Choi said.
"And 14 years later I'm here right now, and I made it. My dreams have come true. It's an amazing day."
Germany's Sandra Gal signed off with a 74 to end up alone in third place at one over, her first top-10 in a Major championship.
Shanshan Feng, the first player from mainland China to win a Major title with victory at last month's LPGA Championship, closed with a 71 to share fourth place at two over with South Korea's Lee Il-Hee (70) and Italy's Giulia Sergas (72).
In pursuit of her sixth victory on the LPGA Tour, Choi made a stumbling start to the final round with a bogey on the opening hole but she maintained her advantage after Yang also faltered there.
Both players birdied the par-four fourth before Yang picked up another shot at the ninth to trim Choi's lead to five.
Choi, who reached the turn in even-par 36, made a complete hash of the par-five 10th where she lost her ball after a wayward drive and went on to record a nervy triple-bogey for her lead to be cut to just two.
However, she responded with a 'bounce-back' birdie at the 11th after hitting a superb approach to five feet to stretch her cushion to three strokes.
Choi did remarkably well to save par at the 12th, sinking a 20-footer after her approach had ended up in thick grass to the left of the green.
The Korean again flirted with disaster with an errant tee shot at the par-three 13th, her ball bouncing off rocks on the edge of a water hazard before ending up behind the green from where she got up and down to save par.
Choi gained welcome breathing room when Yang, her closest pursuer, bogeyed the 14th to slip four shots behind. Both players birdied the par-four 15th but Choi picked up her fourth shot of the day at the 16th to forge five ahead, then finished par-bogey to triumph by four strokes.
"I learned a lot," Yang said after producing her best finish in a Major. "It gives me a lot of confidence that I came in second this week. My game is feeling pretty good and I'm going to keep trying hard."
Taiwan's world number one Yani Tseng, who has claimed five of the last 10 major titles, closed with a second successive 78 to finish in a tie for 50th, a distant 21 strokes off the pace.