His first-team debut for Wolverhampton Wanderers came as a 17-year-old in the 2000–01 season against Sheffield Wednesday at Molineux on 13 August 2000. At the end of his first season, Lescott was named the Supporters’ Young Player of the Year by the Wolves fans; an award he also won in the subsequent 2001–02 season.

Lescott started to become a regular fixture in the Wolves team. During the 2002–03 season he missed only one league match and played in each of the club’s FA Cup fixtures. He was a member of the team that beat Sheffield United 3–0 at the Millennium Stadium in the 2003 First Division play-off Final to win promotion to the Premier League for the 2003–04 season.

In October 2005, Lescott agreed a two-and-a-half-year extension to his contract at Wolves. At the conclusion of the 2005–06 season, he was named in the Championship PFA Team of the Year.

Lescott was sold to Everton at the start of the 2006–07 season for an immediate payment of £2 million, followed by a further £2 million paid in instalments and a final £1 million contingent on appearances. The transfer was slightly delayed as Everton asked for extra medical checks to be taken on Lescott’s knee following the reconstruction of the joint earlier in his career. Lescott made his Everton debut in August 2006 during a victory over Watford and his first start of the season away to Tottenham Hotspur, after Alan Stubbs injured his groin in the previous match against Blackburn Rovers. The match was Everton’s first victory at White Hart Lane in two decades, and Lescott was named man of the match. Lescott started again in the next match, the 204th Merseyside derby, a 3–0 victory for Everton. Lescott’s first Everton goal came in a 1–1 draw against Aston Villa at Villa Park on 2 April 2007. Lescott was voted the Players’ Player of the Season for 2006–07 by his teammates. He also finished second behind Mikel Arteta in the Fans’ Player of the Season.

Lescott has represented England at under-18, under-20, under-21 and B levels. After his first season for Everton, Lescott made his England B debut against Albania at Burnley’s Turf Moor on 25 May 2007, he replaced Reading’s Nicky Shorey in the 74th minute.

On 3 September 2007, Lescott received a call-up to Steve McClaren’s England squad for the UEFA Euro 2008 qualifiers with Israel and Russia. Lescott made his international senior debut against Estonia on 13 October 2007 – replacing Rio Ferdinand at half-time – with England winning 3–0. His second cap – and first start – was the UEFA Euro 2008 qualifier against Russia, which England lost 2–1.

At the end of season awards, Lescott was voted Everton’s Player of the Season and Players’ Player of the Season. Prior to the final home match of the season against Newcastle, on 11 May 2008, Lescott was also awarded the Player of the Year award by the Everton Disabled Supporters Association. The EDSA labelled Lescott “Mr Consistency” for his performances over the 2007–08 season. He is also only the second Everton player to have ever been awarded the honour twice.

The start of the 2007–08 season saw Lescott move to the left-back position after Joseph Yobo and Phil Jagielka’s successful partnership at the centre of Everton’s defence provided manager David Moyes with a selection dilemma. On 7 December 2008, Lescott played superbly against Aston Villa scoring two goals, even though Everton lost 3–2.

Lescott made his first England appearance under the management of Fabio Capello on 26 March 2008 in a friendly match against France, coming on as a substitute at half time for the captain John Terry. He made two appearances in qualifying for the 2010 FIFA World Cup, but injury prevented him from being part of the squad for the finals. Lescott was a regular member of the England squad during qualification for UEFA Euro 2012 and was named in Roy Hodgson’s 23-man squad for the tournament. On 11 June 2012, he scored his first international goal for England with a header against France in England’s opening match of UEFA Euro 2012.

On 25 January 2009, Lescott scored Everton’s only goal – a close-range header – in the FA Cup fourth round meeting with Liverpool. The match ended as a 1–1 draw, but Everton went through by scoring the replay’s only goal in extra-time on 4 February. Lescott played for Everton in the 2009 FA Cup Final at Wembley Stadium on 30 May, resulting in a 2–1 defeat to Chelsea.

Following the end of the 2008–09 season, Manchester City attempted to sign Lescott, but Everton publicly rejected two offers from the club. On 11 August 2009, Lescott submitted a formal written transfer request, which was immediately rejected by Everton. Manager David Moyes refused a request from Lescott to be taken out of the squad for the first home match of the season, a 6–1 defeat to Arsenal. Lescott received a mixed reaction from Evertonians when the teams were announced on the PA system.

The ongoing saga finally came to an end when Lescott moved to Manchester City for a fee speculated to be £22 million with Lescott signing a five-year contract with the club on 25 August 2009. Lescott made his debut for City on 27 August in a 2–0 League Cup away victory over Crystal Palace and scored his first City goal in a 2–2 draw with Fulham on 25 October 2009. Lescott’s first season and a half proved to be a frustrating time for the defender with him struggling to find the form he had shown at Everton, along with picking up a number of injuries, which included re-injuring his knee after hyper-extending it in a 3–3 away draw with Bolton Wanderers. Roberto Mancini replaced Mark Hughes as manager in December 2009 and preferred Lescott after his return from injury to Kolo Touré to partner the fast improving Vincent Kompany for a few months which in this time, including an impressive 4–2 win over Chelsea at Stamford Bridge in March 2010. With Lescott finally showing good form he would once again find himself frustrated after picking up another niggling injury, which would see him struggle to get back into the team in his preferred central defensive role for the foreseeable future.

On 28 December 2010, Lescott scored a header, City’s first of the season, in the 4–0 victory over Aston Villa at the City of Manchester Stadium, but during the January 2011 transfer window, with Lescott making few first-team appearances during the first half of the 2010–11 season, there was speculation that he would be moving back to Wolverhampton Wanderers on loan, Roberto Mancini however continually insisted that Lescott was a part of his plans. In February 2011, Kolo Touré was suspended for failing a drug test, this would represent a huge opportunity for Lescott who was reinstalled as the partner of Kompany in central defence. Lescott went from strength to strength as the two formed a formidable defensive partnership. On 17 April 2011, he started and played the full 90 minutes against Manchester United in the 1–0 FA Cup semi-final victory at Wembley Stadium as City reached their first major-final since 1981. On 25 April, eight days after that win over their rivals, Lescott partnered Kompany again in an important match against Blackburn Rovers at Ewood Park and completing the full 90 minutes in a 1–0 win, also making his 30th appearance of the season for City in the process. Lescott was part of the Manchester City team that won the FA Cup, beating Stoke City 1–0 in the final at Wembley Stadium and ending a 35-year wait for a major trophy in the process. He would also score two more headers in the final two matches of the season, in a 3–0 win against Stoke City three days later and also against Bolton Wanderers in a 2–0 win, as City ended the season in third position and qualified for the UEFA Champions League for the first time.

On 7 August 2011, in the 2011 FA Community Shield at Wembley Stadium, Lescott scored in a 3–2 loss against Manchester United. This would prove to be City’s last defeat on English soil until a 2–1 defeat by Chelsea on 12 December. During this time, Lescott firmly established himself as a vital part of the team in defence as City recorded 5–1 and 6–1 away victories over Tottenham and Manchester United respectively, in which Lescott started both and assisted a goal in the victory over United. Lescott scored an own goal in a 1–1 draw with Liverpool at Anfield in November but continued to show strong form throughout the season. Lescott also made his Champions League debut against Napoli, though City failed to progress past the group stages. On 22 January 2012, Lescott scored a goal in a 3–2 win against Tottenham, giving City a 2–0 lead at the time. He was an unused substitute as City were beaten 1–0 by Wigan Athletic in the 2013 FA Cup Final at Wembley Stadium on 11 May.

In April 2012, Lescott, his brother Aaron Lescott, and now retired defender Jordan Stewart launched a fashion line of high end designer clothes called “The Lescott Stewart Collection.” Lescott is a cousin of British boxer Brian Rose. The pair were featured together on Sky Sports’ Ringside programme in April 2013.

In 2014, Lescott was reportedly offered the chance to leave Manchester City with clubs such as West Ham being linked as prospective destinations, and a deal being agreed at one point. However, Lescott turned down a move to “win trophies” before seeing what happened at the end of the season. Lescott fulfilled his wishes, winning the League Cup and the 2013–14 Premier League.

Despite interest from Hull City and Stoke City, on 20 June 2014, Lescott signed for West Bromwich Albion for free on a Bosman transfer, signing a two-year contract with the option of a further year. He was the first signing for the club by Alan Irvine, with whom he had previously worked at Everton, and he also knew his assistant Rob Kelly from Wolves. He scored his first goal in a 3–2 defeat against Queens Park Rangers. Following six clean sheets in only ten matches under new manager Tony Pulis, Lescott was praised by the fans with some calling for a call-up back into the England squad.

On 1 September 2015, Lescott signed for fellow Premier League club Aston Villa. When signing for Villa, Lescott revealed to the Birmingham Mail he has been an Aston Villa fan from a young age.

Lescott made his debut twelve days later, playing the entirety of a 3–2 loss away to Leicester City. On 5 December, he scored his first goal for Villa, finishing Jordan Veretout’s corner kick to open a 1–1 draw at Southampton. Lescott scored again for The Villans when another of his headers was fumbled by Wayne Hennessey in what proved to be the only goal in a 1–0 win over Crystal Palace on 12 January 2016, just the team’s second win of the 2015–16 season and first of 20 matches, and their first clean sheet since 8 November. On 6 February 2016, Lescott was on the score sheet again in a 2–0 victory over Norwich City, his header finding its way past Declan Rudd from Carles Gil’s corner.

In April 2016, Lescott again angered fans with controversial comments following the club’s confirmed relegation to the Championship after losing to Manchester United. He described the relegation as “a weight off the shoulders” and that they “can give these fans what they deserve – some performances”.

On 29 August 2016, Lescott joined Superleague Greece club AEK Athens on a two-year contract. The 34-year-old defender suffered a detached cartilage in his knee while cycling in his apartment. The injury ruled Lescott out for the remainder of the season. The player refused to get help from the team’s doctors and insisted on completing his rehabilitation in the UK. AEK Athens did not agree to the player’s wishes and additional demands, which resulted in his contract being terminated on 14 November 2016 by mutual consent.

On 24 January 2017, Sunderland signed Lescott on a short-term contract until the end of the season. His departure was confirmed on 9 June 2017.