Born in Penafiel, Fonte finished his football education (after already having played there from ages 10–13) at Sporting CP, but only appeared with Sporting CP B as a senior, in the third division. In 2004 he signed with S.C. Salgueiros, but the club was in severe financial difficulties and was liquidated shortly thereafter; as a result he terminated his contract and transferred to F.C. Felgueiras, in the Segunda Liga.

In the 2005 off-season, Fonte made his Primeira Liga debut with Vitória de Setúbal, where his performances attracted the eye of S.L. Benfica, who signed him in January 2006, immediately loaning him out to fellow league side F.C. Paços de Ferreira; he finished the season with 26 league appearances and one goal – during a 2–2 away draw against F.C. Penafiel where he also scored two in his own net– as both Paços and Setúbal managed to maintain their status.

Fonte was called up to the Portuguese under-21 squad for the Vale do Tejo tournament in 2006. On 24 January he played against Slovenia, as the match ended with a penalty shootout loss after a 1–1 draw.

In 2007, Fonte moved on loan to Crystal Palace in England, being introduced in the side’s starting XI after a run of injuries. The move was made permanent at the end of the campaign, as Palace finished fifth and qualified to the promotion play-offs.

Fonte signed for Southampton on 9 January 2010 for a fee believed to be around the region of £1.2 million, signing a three-and-a-half-year contract. He made his debut one week later alongside two other recent signings, Jon Otsemobor and Danny Seaborne, in a 1–1 draw at Millwall; his first goal for the Saints came on 28 August 2010, in a 4–0 away win against Bristol Rovers.

On 29 December 2011, Fonte signed a new contract keeping him at the club until 2015. Southampton were top of the table when he signed, with the player having appeared in every league game, and he eventually contributed with 42 matches and one goal (against Coventry City in the final matchday) as the side achieved a second consecutive promotion.

Fonte made his debut in the Premier League on 19 August 2012, playing the full 90 minutes in a 2–3 away loss against Manchester City. He netted his first goal(s) in the competition in a 2–2 home draw to Fulham on 7 October, the second arriving in the last minute; on 24 August 2013, he scored a header in the 89th minute of the home game against Sunderland, rescuing a point for his team.

On 23 January 2014, Fonte was attacked by teammate Dani Osvaldo during a training session. Subsequently, the latter was loaned out to Juventus F.C. during the winter transfer window.

On 8 August 2014, Fonte penned a new three-year deal with Southampton running until 2017, and was also named team captain. He made his 250th league appearance for the club on 16 October 2016, in a 3–1 home win against Burnley.

On 3 October 2014, at nearly 31, Fonte received his first call-up to the full side, for a friendly with France and a UEFA Euro 2016 qualifier against Denmark. He made his debut in another exhibition game, playing the second half of a 1–0 win over Argentina at Old Trafford on 18 November.

On 20 January 2017, aged 33, Fonte moved to West Ham United for a reported fee of £8 million (plus potential add-ons) on a two-and-a-half-year deal. He made his league debut on 1 February, in a 0–4 home defeat by Manchester City in which he conceded a penalty by bringing down Raheem Sterling.

On 4 November 2017, after a league match against one of his former teams, Crystal Palace, it was confirmed Fonte had suffered a foot injury that would sideline him for the rest of the year.

Fonte completed a transfer to Chinese Super League club Dalian Yifang on 23 February 2018, joining for a reported fee of £5 million. On 15 July, he terminated his contract.

Fonte moved to French club Lille OSC on 20 July 2018, signing a two-year contract.