Rose held his nerve over the treacherous Merion course to finish on one-over, two strokes clear of Phil Mickelson and Jason Day.
The win means Rose emulates Tony Jacklin's US Open success at Hazeltine in 1970, while he ends England's 17-year wait for a major champion - following Nick Faldo's triumph at the Masters.
Mickelson, who started the final round with a one-shot lead, had to settle for sixth second-placed finish at the US Open.
And following a dramatic final day in Philadelphia, we get the views of all the big names
The new champion admitted that keeping mistakes to a minimum was crucial to claiming his first major title in the US Open at Merion.
"What a day, I just kept telling myself that bogeys is what everyone was doing," he said.
A devastated Mickelson admitted finishing runner-up at the US Open for the sixth-time was "heart-breaking".
He said: "This is probably the toughest for me because at 42, to be so close, you know, it was really set up for me."
The Spaniard ended a turbulent week reflecting on what might have been after finishing well down the field on 15 over.
He said: "Today I didn't hit a big drive at 14. I missed my fairway by probably four yards and I was in the hay. So it's just that kind of tournament."
The world No 1 insisted he had plenty of positives to take away from Merion despite finishing at 13 over par.
He said: "There's always a lesson to be learned in every tournament whether you win or lose. I'll look back at the things I did right and the things I did wrong."
The former champion admitted he let his frustration boil over after he bent the shaft of one of his irons during the final round.
He said: "I think that's what this tournament does to you. At one point or another it's got the better of you, and it definitely did this weekend."
The Scot launched an angry attack on the USGA over the "ridiculous" set-up of the Merion course.
"From 14 on is the hardest finish in golf I've ever played," he said. "It really is just brutal. There's out of bounds in play on a couple of the holes, it's 250-yard par threes with pins that are on slopes."