Lee Sharpe began his footballing career at Torquay United, and in his first season with them, after only 16 games, Manchester United noted his potential and swooped to sign him for £200,000, a record fee at the time for an YTS player.  He soon broke into the first team, initially playing out of position at left back before replacing Ralph Milne as left-winger in the 1990–91 season. He played a key part in United's success in the European Cup Winners' Cup that season, and he scored a hat-trick against Arsenal at Highbury in the League Cup with United eventually winning the game 6–2. Lee himself cites this as one of the best memories in his footballing career. During eight years at Old Trafford he played 265 games and scored 36 goals. Despite his injury history, Leeds United signed him for £4.5 million in the summer of 1996, making him their record signing. However his time at Leeds was beset by further injuries. He was restricted to 26 Premiership appearances in 1996–97, scoring five goals, and then a pre-season knee injury ruled him out for the entire 1997–98 season after which he was unable to regain his place in the team. In the autumn of 1998, he was loaned to Italian Serie A side Sampdoria until early 1999, and then in March went on loan to Bradford City helping in securing the club's promotion to the Premiership after 77 years outside the top division. He then joined Bradford on a permanent deal for a £250,000 fee during the summer and helped preserve the club's Premiership status in the 1999–2000 season.

In 2000–01, Lee lost his place in the Bradford team and just before Christmas went on loan to Division One Portsmouth. He returned to Bradford during the 2001–02 season and when his contract expired he was given a free transfer. Following a brief trial stay with Grimsby Town he signed for Exeter City, and then followed this with a short spell at Grindavík FC in Iceland. Then in June 2003 he announced his retirement from professional football at the early age of 32.

After leaving the game Lee developed a career in television, especially in reality TV shows. His boundless charm and keen sense of humour coupled with a natural ability in front of the cameras have ensured that since his retirement from a very successful football career he is in demand as a guest, presenter, interviewee and celebrity contributor across all media platforms. Television work has included the 2005 ITV television show Celebrity Wrestling, where he appeared as a competitor under the name "Sharpe Shooter". Although, he may be best known for appearing in Celebrity Love Island along with Abi Titmuss. He was a contestant in ITV's Dancing On Ice where he partnered Frankie Poultney, and made it through to round seven, and also starred in Dec's team on Ant versus Dec, on their Saturday Night Takeaway Show. More recently he appeared in the 2008 television series Superstars on Channel Five as a member of the winning team captained by Sir Steven Redgrave. Lee now brings his fun outlook on life to the after dinner circuit with numerous stories from the world of football and television, about the characters and personalities he has worked with.