Distin started his career at French non-league side Joue-les-Tours before moving to Tours a year later, where he played 26 times and scored three goals. He then transferred to Gueugnon of Ligue 2, signing his first professional contract. With Gueugnon he won the Coupe de la Liguee in 2000. His performances for Gueugnon prompted Paris Saint-Germain to sign him, though his time at PSG was short-lived and after a year, Distin went on loan to Newcastle United where he made 35 appearances.
Following the loan spell, Newcastle wanted to sign Distin permanently, but he instead opted to sign for Manchester City where he could play in his preferred position of central defence, rather than left-back at Newcastle. The transfer fee was £4 million, setting a club record for a defender. Consistent performances in his first Manchester City season resulted in Distin being named the club's Player of the Year for the 2002-03 season. At the start of the 2003-04 season, Distin was named captain of Manchester City following the retirement of Ali Benarbia. In total, Distin played 207 times for Manchester City and scored six goals.
Distin left City at the end of his contract in May 2007, seeking a "fresh challenge" and moved to Portsmouth on a three year deal. Distin was appointed vice captain by Harry Redknapp and lead Portsmouth in Sol Campbell's absences due to injury. At the end of Distin's first season at Fratton Park, he won his first major honour in English football, the 2008 FA Cup.
After Sol Campbell's departure from Portsmouth, Distin was named the new club captain. In August 2009, Everton signed Distin from Portsmouth for a fee of about £ 5 million. Distin wears the number 15 shirt at Everton and made his debut in a 2-1 victory over Wigan Athletic. On 17 September 2009 he scored his first goal for Everton in the UEFA Europa League against Greek team AEK Athens.