In September 2006, Topal joined Süper Lig powerhouse Galatasaray SK, moving to the club alongside Japanese Junichi Inamoto.

In April 2008, Topal extended his contract with Gala for five years, having played 26 matches during the campaign to help the team win the national championship and also reaching the Turkish national team in that timeframe. In the 2008 summer transfer window, there were rumours surrounding a move to Everton in the Premier League, with David Moyes apparently keen to bring the player to Goodison Park.

Topal earned his first cap for Turkey on 6 February 2008, coming on for Emre Belözoğlu in the 78th minute of a 0–0 friendly home draw with Sweden. Shortly after, he was selected by manager Fatih Terim for his UEFA Euro 2008 squad, playing all the games in Austria and Switzerland but one for the eventual semi-finalists.

Topal signed for Valencia CF on 12 May 2010, for a fee believed to be in the region of €5.5 million. On 14 September, he made he first UEFA Champions League appearance with his new club, playing the full 90 minutes against Turkish side Bursaspor in a 4–0 group stage win.

Topal scored his first goal with the Che at Sporting de Gijón, on 25 September 2010 (2–0). In the UEFA Europa League, he netted the game’s only goal away against Stoke City on 17 February 2012 in the round of 32 to take his side through 2–0 on aggregate; the 30-yard strike was widely regarded as one of the best goals of that tournament. He contributed with six games to help his team reach the semifinals of the latter competition, but overall played second-fiddle to legendary David Albelda during his stint even though the former was ostracized by manager Unai Emery for a period of time.

On 1 July 2012, Topal moved to Fenerbahçe SK for a reported fee of €4.5 million. He signed a four-year contract with a €2 million annually salary, plus bonuses. He contributed with 27 games and three goals in his second season, as the club won the national championship after a three-year wait.

On 11 August 2015, whilst he drove home after training accompanied by youth player Uygar Mert, Topal’s car was shot at by unknown men. He appeared in 11 games in the Europa League round-of-16 run and, precisely in that stage, against S.C. Braga, he scored the only goal in the first leg at the Şükrü Saracoğlu Stadium; in the second match, he was sent off for two bookable offenses – the second of which resulted in a penalty – as his team had a further two players ejected in an eventual 4–2 aggregate loss.

On 22 May 2016, Topal captained the nation for the first time, in their 1–2 friendly loss to England at the City of Manchester Stadium. A week later, he scored his first international goal on his 58th cap, the only one of a last-minute victory over Montenegro in Antalya. Picked for Euro 2016, he started in all the matches, featuring as a central defender in a 0–3 group stage defeat against Spain.

On 26 June 2019, the 33-year-old Topal left by mutual consent.

On 26 August 2019, Topal joined İstanbul Başakşehir F.K. on a two-year deal, the latter one being optional. After conquering the domestic league at the end of the campaign, he became the first footballer to achieve the feat with three different teams.