Rose, 29, trailed the 21-year-old Fowler by four strokes entering the final round and closed with a 6-under-par 66 at Jack Nicklaus’s Muirfield Village Golf Club in Dublin, Ohio.
Rose, who is 66th in the world golf ranking, finished 18- under for the tournament and receives $1.08 million. Rose’s five previous titles came outside the U.S., where he had five top-10 finishes in the past three years, including a runner-up showing at the Memorial in 2008.
“I’ve had a few close calls over time and you start to sometimes wonder why you can’t get it done,” Rose, who was playing his 162nd PGA Tour event, said in a televised interview. “It’s nice to have the hard work pay off.”
Fowler, a rookie making his 24th PGA Tour start, finished 15-under after a final-round 73.
Defending champion Tiger Woods tied for 19th at 6-under in his first event following a three-week layoff due to a neck injury. He shot rounds of 72, 69, 69 and 72 in his final tune-up before the U.S. Open.
The PGA Tour next moves to Memphis, Tennessee, for the $5.6 million St. Jude Classic at TPC Southwind from June 10-13. It’s the final event before the U.S. Open at Pebble Beach Golf Links in California. The season’s second major championship begins June 17.