The son of actor and producer Michael Lester and actress Rita Lester, Mark attended Corona Stage School in London and had supporting roles in several British television series, including The Human Jungle and Danger Man. At the age of nine Lester was cast in Oliver! (1968). He played the lead in the multiple Academy Award winning musical adaptation of Charles Dickens' novel, which co-starred Jack Wild. These two child actors later reunited for Melody (1970), which depicted British schoolchildren in love. Tracy Hyde played the role of Melody in the film, which was scored by early music from the Bee Gees and Crosby, Stills, Nash & Young.

Lester received critical acclaim for his portrayal of a withdrawn only child in Run Wild, Run Free, starring opposite Sir John Mills. However, after starring in Black Beauty (1971), he found good roles harder to come by. Night Hair Child and Redneck were considered by many critics as inappropriate vehicles for the young actor. After making The Prince and the Pauper at the age of 18 (which reunited Lester with Oliver Reed from Oliver!) he stopped acting and became addicted to alcohol and drugs. Having exhausted his earnings, he later took his A Levels at the age of 28 and became an osteopath. He married in 1993 but filed for divorce in 2004, with both sides accusing the other of destroying the marriage through excessive drinking and not putting forth effort.

Lester is a close, long-time friend of the troubled pop superstar Michael Jackson, and spent Christmas 2003 at the Neverland Ranch. While Lester was willing to testify in Jackson's defense at the trial, he was not called to do so. Lester has consistently supported his friend by telephone and in interviews.

Lester should not be confused with film director Mark L. Lester.