Butch Harmon was raised in New Rochelle, New York; his father was the head pro at the nearby Winged Foot Golf Club. The family also lived part of the year in Florida, when Butch's father served as the winter professional at the Seminole Golf Club. Butch began playing golf from an early age, as did his three younger brothers, Craig, Bill, and Dick, who also all became golf professionals. Butch graduated from Iona Grammar School and then New Rochelle High School. Butch excelled at all sports, and was a star halfback on the 1961 New Rochelle High School football team that compiled a 5-2-1 record.

Harmon attended the University of Houston, and served in the U.S. Army for three years, seeing duty in the Vietnam War. Harmon was a PGA Tour player from 1969 to 1971, with one win to his name on the Tour, the 1971 Broome County Open. He lived in Morocco for several years in the 1970s, serving as the personal instructor to King Hassan II. He was a club professional in the United States, and became well-known through his work with Greg Norman, beginning in the early 1990s.

Harmon is best known for having been Tiger Woods' golf coach from 1993 to 2004, though they have since gone their separate ways. In April 2007, it was announced that Harmon would start working with Phil Mickelson. He has also worked with other major champions such as Ernie Els, Stewart Cink, Greg Norman, Davis Love III, Fred Couples and Justin Leonard, and with younger stars such as Nick Watney, Adam Scott, Dustin Johnson, and Natalie Gulbis.

In 2003 Harmon was ranked the top golf teacher in the United States in a poll of his peers organized by Golf Digest magazine, and has repeated as winner of this honour each year since. He runs the Butch Harmon School of Golf at the Rio Secco Golf Club in Las Vegas, Nevada in the U.S. He also gives golf clinics around the world.

On April 8, 2008, Ernie Els officially announced that he was switching swing coaches from David Leadbetter (whom Els had worked with since 1990) to Butch Harmon. During Els' 2008 Masters press conference, Els said the change was made to try to shorten and tighten his swing, as well as get a fresh perspective.

Harmon's brothers Craig and Bill are also both top golf coaches, who have made the top 50 Instructors' list compiled by Golf Digest on several occasions. Butch's other brother Dick was the golf professional at the River Oaks Country Club in Houston, Texas from 1977 to 2001. After leaving that position, he established two teaching centers in Houston. Dick died February 10, 2006 at age 58.

Harmon appears regularly in the media, including work for Britain's Sky Sports. Commentating for Sky Sports at the 1997 Ryder cup, Harmon was asked about the negative press Nick Faldo was receiving from the media in the build up to the event. Harmon replied, "How can you not like Nick Faldo? He's one of the greatest golfers of all time and he's also one hell of a nice guy."

Butch Harmon wrote the 2006 book The Pro, describing his life in golf with his father, brothers, friends, and the top players he has coached.

Harmon has written golf instructional books under the titles Four Cornerstones of Winning Golf and Butch Harmon's Playing Lessons. He also worked with Greg Norman on his multi-media learning system Greg Norman's Better Golf, which consists of three videos, a book, skill guide cards, and an audio tape; as well as on Greg Norman's book Advanced Golf. Harmon writes a regular monthly instructional column in Golf Digest magazine.