Anastasiou, 40, has been given the task of trying to restore the fortunes of the Athens club after a season of struggle financially and on the pitch.
The former Greece international, whose appointment was announced on April 24, replaces Giannis Vonortas, who will return to coaching the academy youth side after acting as caretaker coach for the final few weeks of the season.
"It's a great honour and responsibility to be given this chance, the goal of the club is to operate at the highest European level and to do this the club must use its own philosophy, not something based on other foreign clubs in England or Germany," Anastasiou told a news conference.
"You will not hear any big, blown-up statements from me or my colleagues," he added. "We want to become better and develop in all areas as a club. We know that a lot of hard work is required and we are ready for it
"All we can promise is that we will maximise our hours out on the training pitches to do the best we can to improve the team."
Anastasiou's support team will feature former Panathinaikos and Greece player Dimitris Sarravakos, former Greece international Nikos Dabizas and Englishman Steve Rutter, the former coach education manager at the Football Association (FA).
Anastasiou, who had a successful playing career in Greece, the Netherlands and Belgium, was assistant coach at Panathinaikos from 2008-10 under Dutch coach Hen Ten Cate and was first-team coach at English Premier League side Reading from January to March this year.
He faces a challenging assignment after Panathinaikos went through four coaches in a dreadful campaign and failed to qualify for Europe for the first time since 1997.
Vonortas was in charge for the final three matches, having followed Spanish coach Fabri, Argentine Juan Ramon Rocha and Portuguese boss Jesualdo Ferreira.
The season was supposed to be the start of an optimistic new chapter under fan ownership after the transfer of the Vardinoyiannis family's majority shareholding to the new 'Panathinaikos Alliance' was completed last year.
However, under president Giannis Alafouzos, the club have continued to struggle financially and were forced to sell several Greece internationals such as Kostas Katsouranis, Loukas Vintra, Nikos Spiropoulos and Lazaros Christodoulopoulos.
To make matters worse, arch-rivals Olympiakos Piraeus wrapped up their 40th league title with embarrassing ease in mid-March while Panathinaikos finished 37 points behind their neighbours after their worst season on record.