Stupples tournament total of 19-under-par 269 tied the tournament record on a par-72 course. Karrie Webb set the original mark in 1997 on this same venue, Sunningdale Golf Club. Stupples' total also matched the lowest score in an LPGA Tour major, which Dottie Pepper set in 1999 at the Nabisco Dinah Shore.
Rachel Teske, who shared the lead after three rounds with Heather Bowie, posted a 2-under 70 to end alone in second place at 14-under-par 274. Bowie managed a final round 71 to finish at minus-13, while 2003 LPGA Tour Rookie of the Year Lorena Ochoa closed with a 70 to come in at 12-under-par 276.
Stupples, who won the Welch's/Fry's Championship in March, started her round one stroke behind the leaders, but quickly erased that deficit. She opened with an eagle at the par-5 first.
The Englishwoman then holed her 5-iron second shot at the par-5 second for a double-eagle. Stupples quickly jumped into the lead at 16 under.
'I knew I needed to get off to a good start today,' said Stupples, who became the first Englishwoman to win a major since Alison Nicholas in 1997. 'I was really anticipating just birdie, birdie or something like that would have done quite nicely. On the second, it was just a nice yardage for me to hit and it was right on line all the way. Unfortunately I didn't see it go in the hole, but the cheer from the crowd was absolutely unbelievable and really could not come at a better time.'
Teske meanwhile was not going away quietly. She birdied the first and second to get to 14 under. Stupples dropped a stroke with a bogey at the par-4 sixth. Teske then tied her in the lead at minus-15 when she rolled in a birdie putt at the seventh.
Stupples moved back into the lead with a birdie at the 10th, but Teske matched that birdie to forge another tie at minus-16. The next few holes turned out to be the turning point in the tournament.
Stupples made it two in a row when she birdied the 11th. However, she tripped to a bogey on 12. Teske, with a chance to take advantage of Stupples' mistake, was unable to do any damage. She bogeyed the 12th as well to remain one behind Stupples.
The 30-year-old Stupples took over down the stretch. She rolled in a birdie putt at the 15th to get to 17 under. Teske dropped to 14 under with a bogey at the 15th.
'I knew when that went in, all of a sudden I had a three-shot lead, and then it was down to Rachel to try and catch up,' said Stupples of her birdie at the 15th. 'I had not really made too many mistakes over the tournament and I felt like I was really hitting the ball very well.'
It was all Stupples coming home. She drained another birdie putt at the 16th to move four shots clear of the field. Stupples capped a magical round with her third straight birdie at the 17th. She parred the last to match the tournament scoring mark.
'I was a little tentative,' Stupples said. 'I think it was some from Saturday creeping into today's round because I was trying to be too precise. I knew it was important for me to try and keep the pressure on Rachel and to make sure that I was in the lead.'
Stupples' best finish in a major prior to this win was a tie for ninth at the 2002 McDonald's LPGA Championship. Her best previous finish at this event was a tie for 12th last year.
Teske parred her final three holes to match her best showing in a major. She had previously tied for second at the Kraft Nabisco Championship in 2001.
'I started off well with two birdies on the first two holes and then birdied seven,' Teske said. 'I didn't have a taste for the putts too well on the back nine but hung in there and closed with some good shots on last three holes so that was good. Obviously, Karen's round, you couldn't ask for any better being British and being able to do it in your home Open. That would be a dream of all of us.'
Bowie got into the mix as she collected three birdies over her first 10 holes to climb to 15 under. However, she faltered to bogeys at the 12th and 16th to drop off the pace.
Michele Redman fired a 6-under 66 to climb to 11-under-par 277. She was joined in a tie for fifth by Giulia Sergas (67) and Beth Daniel (68).
Minea Blomqvist, who set the course record of 10-under 62 on Saturday, birdied her first two holes Sunday. From there she posted three bogeys, one birdie and a hole-out eagle at the par-4 ninth to finish at minus-10. She was tied there by Jung Yeon Lee and 1986 Women's British Open champion Laura Davies.
Annika Sorenstam, the 2003 champion, closed with a 1-under 71 as she carded four birdies and three bogeys. She finished in a tie for 13th at 8-under-par 280. Sorenstam was attempting to win her fourth separate major championship in back-to-back years, something only Mickey Wright has done.