On 22 July 2014 Vrsaljko signed for Serie A side Sassuolo for €3.5 million plus bonuses of €2 million. He became a key part of Sassuolo's defence under manager Eusebio Di Francesco, and eventually helped the team to achieving their first ever Europa League qualification after finishing 6th in Serie A courtesy of a Juventus Coppa Italia win over Milan as Milan would have gone to Europe instead if they had won the final.