Kim defeated 17-year-old amateur Morgan Pressel, who was tied for the lead in the 18th fairway until Kim's hole-out, and 19-year-old amateur Brittany Lang by two shots.
Kim shot a 1-over 72 in the final round to finish the championship at 3-over-par 287.
Pressel, who shared the third-round lead, managed a 4-over-par 75 to join Lang, who fired an even-par 71, at plus-5.
Michelle Wie, the 15-year-old amateur who was part of the three-way tie with Pressel and reigning Women's British Open champion Karen Stupples, struggled badly on Sunday. She shot an 11-over 82 and tied for 23rd at plus-12.
'I haven't played this bad in a long time, so I definitely learned a lot of things from today,' said Wie, who finished second two weeks ago at the LPGA Championship. ''Difficult' would be too easy a word. It was really hard out there for me today.'
Wie double bogeyed the first when her drive landed in the left rough and it was all downhill from there. She finished out her front nine at 7-over 42, then had four bogeys, two birdies and a double bogey in a 4-over 40 on the back nine.
Annika Sorenstam never made a run in her quest for the third leg of the single-season Grand Slam. The Swede posted a 6-over 77 and was part of the group tied with Wie.
'I am disappointed, but I am going to leave here and I am going to know in my heart that I gave it all, it just did not happen,' said Sorenstam. 'Having said that, that just gives me something to work on. That's not a bad thing.'
Kim and Pressel were tied at 4 over par when Kim stepped on the tee at the 18th. The hole was ranked as the hardest in U.S. Women's Open Championship history and certainly claimed its victims on Sunday.
Lorena Ochoa reached 3 over par for the tournament thanks to four birdies on the back nine. Her drive at 18 was awful, as her club hit the ground first, then sent the ball short and left in the water.
Her third shot, once again from the tee, landed in the right rough, forcing her to chop out to the fairway. Ochoa's fifth hit the ground hard and bounced into the grandstands. She got a free drop and her sixth came up 10 feet short of the pin, where she missed for a quadruple-bogey and a 7 over-par total.
'I just gave the tournament away,' admitted Ochoa. 'I had a pretty good chance and I was feeling really good. I tried really hard and tried to do my best and I was fighting a lot for 71 holes, and all of a sudden just in the last one, you give everything away. It is a humble game, you have to learn from it.'
Next one to be humbled at the 18th was Natalie Gulbis. She was at 5 over par and with a par would have been the leader in the clubhouse. Gulbis' approach at 18 landed in the same bunker that Kim's ball would find one hour later.
Gulbis blasted out to 5 feet and her par putt never broke the way she thought.
Lang was up next and landed in that familiar sand trap. She blasted her third to roughly the same spot Gulbis found, and the result was the same. Lang missed the par putt right, so she got into the clubhouse at 5 over par.
'It's pretty exciting,' admitted Lang, who will turn professional at the end of the summer. 'I didn't look at the leaderboard all day, so I didn't really know exactly where I stood. I was happy with my week so I wasn't disappointed she made that bunker shot.'
Kim and Pressel separated themselves on the back nine, but due to Cherry Hills' difficulty, they came back to the pack.
Kim went ahead with a 12-foot birdie putt at the 11th, but ran into trouble at No. 14 when her drive was less than a foot from being out of bounds. She punched her second into the fairway, then knocked her third 20 feet right of the flag. Kim missed the par putt short, but tapped in for bogey.
Pressel was in trouble one hole behind. Her drive at 13 found the left rough, then her second came to rest in a front bunker. She blasted out to 4 feet, but Pressel missed the putt. She did hole a clutch par save at 15, but Kim had control of the tournament.
Kim was ahead by one shot until her tee ball at the par-4 16th ran into the rough. She pitched out with her second and hit her third from 133 yards out 40 feet short. Kim's par putt came up 3 feet short and it was a bogey, putting the two in a tie.
Both Kim and Pressel had makeable birdie putts at the par-5 17th. Kim, one group ahead of Pressel, missed her 20-footer, then the 17-year-old amateur failed from almost the same spot.
At the 18th, Kim drove into the fairway and hit a seven-wood into the right bunker. Her blast from the trap checked a bit, then rolled right into the cup for the amazing birdie.
'I didn't think of making, I just tried to get close,' said Kim, who pocketed $560,000 for the win. 'I tried my best to get par.'
In the fairway, Pressel looked on in disbelief.
'Anytime you miss the green there you don't know what to expect,' said Pressel. 'She hit a great shot. I was like, 'I can't believe this is happening to me.''
Pressel came up short and right with her approach, but if the ball landed a few feet more to the left, it could have rolled near the hole. Her pitch sailed long and right and Pressel threw her club at her bag in disgust.
She missed the par putt to tie fellow amateur Lang.
'It's positive I finished second in the Open, but I mean it was the fact that I was just so close,' lamented Pressel. 'If a couple of bounces would have gone my way, it would have been mine, but it's not.'
Kim collected her first LPGA Tour victory in her 34th start. She became the third player in tournament history to win this prestigious event in her first try.
Gulbis finished with an even-par 70 and tied for fourth with Lorie Kane, who fired a 2-under 69. The duo came in at 6-over-par 290.
Ochoa carded a 1-over 72 on Sunday and tied for sixth with Karine Icher (72), Candie Kung (74) and Young Jo (76) at 7-over-par 291.
Stupples struggled in the final round and shot a 7-over 78. She shared 10th place with Cristie Kerr (75) and Angela Stanford (76) at 8-over-par 292.
Defending champion Meg Mallon finished with a 2-over 73 and tied for 13th at plus-9.