San Lorenzo striker Franco Di Santo tasted English football for the first time when he signed for West London giants Chelsea in 2008. The Blues paid around £3.4m to secure his transfer from Chilean club AudaxItaliano. He moved to the Premier League as a hot prospect.

Franco Di Santo signed for the Blues as a teenager but he was unable to break into the starting XI at the club. In the end, he moved to Wigan Athletic for £2m on the back of his loan spell at Blackburn Rovers. He was on loan at Blackburn Rovers from Chelsea for the 2009/10 season before the Latics made the decision to sign him on a permanent deal in 2010.

His debut for Wigan Athletic came in the Premier League encounter with Sunderland. Franco Di Santo came on for Hendry Thomas with 54 minutes on the clock. The two teams played out a 1-1 draw. He was given his first start at Wigan Athletic in the next game, a 2-0 loss to Manchester City at home in the league.

His first goal in a Wigan Athletic shirt came in the 4-2 defeat at Sunderland in the league game played in April 2011. He had made his debut for the club in the reverse fixture. Franco Di Santo scored the last goal of the game in added having come on for the last seven minutes of the game in the place of Frenchman Charles N'Zogbia. The goal was his first since October 2009. He had gone almost two years without finding the back of the net.

In the following Premier League season (2011/12 season), Di Santo won a penalty in the first game of the season against Norwich City and it was converted by teammate Ben Watson. In the third game of the league season, the Argentine scored twice for Wigan in a 2-0 win at home to London club QPR. In total, Franco Di Santo scored 13 goals in the Premier League in the colours of the Latics in 92 games before signing for Werder Bremen in the German league in 2013.