He began his career at Crystal Palace, playing regularly in four Championship seasons, before a move to Southampton in 2012, where he spent three seasons in the Premier League. He joined Liverpool in July 2015 for a fee of £12.5 million.
Clyne was born in Stockwell, London. He made his first-team debut for Crystal Palace in a 3–0 Championship win against Barnsley at Selhurst Park on 18 October 2008. He signed a three-year professional contract with the club two days later, with manager Neil Warnock stating that Clyne "has a bright future in the game". His first career goal came on 8 December 2009, when he opened a 4–2 win at Reading in the seventh minute. In February 2010 he was offered a move to Premier League side Wolverhampton Wanderers, but rejected it without even entering talks with manager Mick McCarthy.
In the 2010–11 season, Clyne was the youngest player in the Football League to play every single game of that campaign, and won Crystal Palace's Player of the Year award.
On 19 July 2012, Clyne signed a four-year deal with newly promoted Premier League side Southampton. He made his debut on 19 August, in a 3–2 defeat against Manchester City at the City of Manchester Stadium. His first game at St Mary's came six days later in a 0–2 defeat to Wigan Athletic. He scored his first goal for the club on 22 September, in a 4–1 win at home against Aston Villa, set up by Gastón Ramírez with England under-21 coach Stuart Pearce in attendance at St Mary's. His second goal for the club came in the FA Cup third round against Burnley on 4 January 2014, opening an eventual 4–3 home victory with a 25-yard strike past Tom Heaton.
Clyne scored in Southampton's first game of the 2014–15 season, a 2–1 defeat against Liverpool at Anfield on 17 August. He scored his second goal of the campaign on 23 September, with a long-range effort which gave Southampton a 2–1 victory at Arsenal in the League Cup third round. On 24 November, he finished Ryan Bertrand's 81st-minute cross to earn a 1–1 draw away to Aston Villa.
On 1 July 2015, Liverpool confirmed the signing of Clyne from Southampton for £12.5 million on a five-year contract, with his former club, Crystal Palace receiving a payment of £2.5m. Clyne made his debut in a Liverpool shirt against the True Thai Premier League All Stars in Bangkok on 14 July as part of the club's pre-season tour. He made his competitive debut on 10 August in a 1–0 away win against Stoke City in the first match of the 2015–16 Premier League season.
On 8 October 2015, Clyne scored his first Liverpool goal in a 1–0 League Cup fourth round victory over Bournemouth; the team's first win under Jürgen Klopp. His first league goal came on the 14 February, in a 6–0 win at Aston Villa.
In March 2016, in Liverpool's first European games against rivals Manchester United, Clyne won a penalty that Daniel Sturridge converted in the first leg, and conceded a penalty scored by Anthony Martial in the second, as Liverpool won 3–1 on aggregate in the last 16 of the UEFA Europa League. On 18 May, he played the full 90 minutes in the final, a 3–1 loss to Sevilla in Basel.
On 2 October 2014, Clyne was named in the England squad for the UEFA Euro 2016 qualifiers against San Marino and Estonia later that month. He was an unused substitute in both matches. Clyne said "My aim, now, is to try to make myself first choice for Euro 2016. That’s what I’m going to keep pushing for." On 15 November, he made his full international debut in a home qualifier against Slovenia, playing the full 90 minutes of a 3–1 victory. Clyne went on to establish himself as first choice right-back for England, appearing in five of their last six qualifiers.
- As of match played 16 September 2016
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- Appearances in UEFA Europa League
- As of match played 20 June 2016