The 27-year-old edged past world No. 1 Scottie Scheffler and Will Zalatoris by a single shot following an enthralling, roller coaster battle with the American duo in Brookline, Massachusetts.
Victory sees the world No. 18 make history as only the second player -- and the first non-American -- to win both the US Amateur and US Open at the same venue, having won at The Country Club in 2013. Jack Nicklaus is the only other golfer to have achieved the feat following triumphs at Pebble Beach in 1961 and 1972.
It also secures Fitzpatrick a $3.15 million share of the $17.5 million total prize, the largest pot in major championship history.
A seven-time winner on the European Tour, Fitzpatrick ended his wait for a major title with a stunning display, not once scoring above par in any of his four rounds despite periods of wind that rocked much of the field playing the challenging par-70 course.
His 68, 70, 68 across the first three rounds saw him arrive as co-leader alongside Zalatoris heading into the deciding day, where his third 68 was enough to claim a one-stroke win at 6 under par.
"The feeling's out of this world," Fitzpatrick told reporters.
"It is so cliche, but it's stuff you dream of as a kid. To achieve it, I can retire a happy man tomorrow."
Born and raised in the Yorkshire city of Sheffield, Fitzpatrick couldn't resist drawing comparisons with his beloved football team, Sheffield United.
"I'm the same deal -- not expected to do well, not expected to succeed," he said.
"I feel like I certainly work hard for it, and where I've grown up that's the mentality of everyone around there ... an underdog mentality. You work for what you get."
More major agony for Zalatoris
Narrow defeat made for yet more heartbreak for Zalatoris, who has now finished runner-up in three majors in recent years. The 25-year-old missed out on the Masters by a single stroke in 2021, before suffering a playoff defeat to Justin Thomas at the PGA Championship in May.
Despite losing by the same margin of error, Zalatoris said Sunday's narrow loss would take longer to process than the one at the Masters.
"It stings," Zalatoris told reporters. "We're obviously doing the right things.
"I'd pay a lot of money for about an inch and a half, and I'd probably be a three-time major champion at this point.
"This one hurts in particular pretty hard, but it's motivating. I've got to keep doing what I'm doing. I know I'm going to get one sooner or later."
Meanwhile, Scheffler narrowly missed out on elevating his spectacular calendar year with a second major victory, having won at the Masters in April and adding three further PGA Tour wins.
With his two 3-under 67's lower than any of Fitzpatrick's rounds, the world No. 1 may come to rue a grim, wind-affected spell through Saturday's penultimate round that saw him drop five shots across a four-hole stretch.
"This week I hit some of the worst shots I've hit in my career, and I've hit some of the best ones, so it was kind of a roller-coaster weekend," Scheffler told reporters.
"Tip of the hat to Fitzy. He's been playing really good golf and he definitely deserved