Butler attended Robert E. Lee High School in Jacksonville, Florida, and played under the direction of the all-time wins leader for a high school football coach in the state of Florida's history, Corky Rogers. Rogers has coached at both Robert E. Lee High School from 1972–1988, where he coached Butler and fellow NFL star Edgar Bennett, and from 1989–present at The Bolles School in Jacksonville, now having won a total of 8 football State Championships. Before moving onto Florida State, Butler was an outstanding player for the Robert E. Lee High School Generals football program.
Butler played under head coach Bobby Bowden at Florida State University. He was a three-year starter, collecting 194 tackles and 9 interceptions, but he's most remembered by FSU fans for his role in the, "puntrooskie." In 1988, against rival Clemson, FSU was backed up to its own 21-yard line, on fourth down, with a minute and 30 seconds left to play and the score tied at 21. Bowden called the famous trick play, a fake punt. The snap went to upback Dayne Williams and he slipped the ball to Butler, who ran 78 yards to set up the game-winning field goal.
Butler was selected by the Packers in the second round of the 1990 NFL draft. He played in 181 games, earned a Super Bowl ring, for Super Bowl XXXI, following the 1996 season, was selected as an All-Pro four times and was selected to the Pro Bowl four times (1993, 1996, 1997, and 1998). He was named to the 1990s NFL All Decade Team, by the Pro Football Hall of Fame, and was later inducted into the Green Bay Packers Hall of Fame, in 2007.
After being selected to his first Pro Bowl, the emphasis of his first name was questioned by sports commentator John Madden, who was told by Packers running back Edgar Bennett that his name is pronounced ("LEE-Roy"); but, after hearing a broadcast, Butler's mother sent an e-mail to Madden describing the emphasis as ("L'ROY"). During his 12 seasons with the Packers, he recorded 953 tackles, 38 interceptions, 553 return yards, 12 fumble recoveries, 3 defensive touchdowns and 20½ sacks. He led or tied for the team lead in interceptions in five different seasons. He was the first defensive back in NFL history to gain entrance in the 20 Sack/20 Interception Club.
A broken shoulder blade sustained while tackling Atlanta Falcons running back Jamal Anderson in the 2001 season forced him into retirement just before the 2002 season when it was discovered it had not healed properly.
Butler is credited with inventing the Lambeau Leap - a touchdown celebration in which the scoring player leaps into the arms of awaiting fans in the stands near the end zone. On December 26, 1993, the Packers were playing the visiting Los Angeles Raiders. On a second-down swing pass to running back Randy Jordan, Butler forced a fumble that was recovered by Reggie White at the Raiders' 35-yard-line. After running with the ball for 10 yards, White lateraled to Butler, who ran the remaining 25 yards into the end zone and then made a spontaneous leap into the arms of fans in the south bleachers. The Packers went on to win 28-0 to clinch what would be the first of six consecutive playoff berths. The move was later popularized by wide receiver Robert Brooks, who carried it a step further by leaping completely into the stands. This move is called the Lambeau Leap and now is used after most Packer touchdowns scored at Lambeau Field.
From 2009 to 2012, Butler owned a Ford dealership named LeRoy Butler Ford in Waupaca, Wisconsin. However, it was sold in 2012.