Spanoulis' transfer to Olympiacos from Panathinaikos in the summer of 2010 marked a new step in his career, given Olympiacos' feisty rivalry with Panathinaikos. Within a young and rebuilding Olympiacos team, Spanoulis not only led the club to a EuroLeague title run in 2012, but he also went on to lead the team to a historical EuroLeague championship repeat in 2013. In the process, he gained another two EuroLeague Final Four MVP awards, thus joining Toni Kukoč as the only players in the history of European basketball to achieve that distinction on three occasions. Under his leadership, Olympiacos reached another two EuroLeague Finals, in 2015 and 2017.