Anastasiou was named manager of Panathinaikos in May 2013. In his first year, the team won the Greek Football Cup with a 4–1 victory against PAOK in the final. During that year, he also led the team in a 3–0 victory against Olympiacos, a record away victory in the derby. In the Superleague Greece, the team finished fourth in the regular season and first in the play-offs, qualifying for next year's UEFA Champions League third qualifying round. In February 2015, he was named Manager of the Year for 2014.