Antonis Nikopolidis was born in Vigla, Arta where he made his first football steps. His first professional club was Anagennisi Artas, which he left in 1989 to continue in Panathinaikos at the age of 18. He played both in Panathinaikos, as well as Olympiacos, and has served as a captain for both clubs, winning several titles with both. The highlight of his career was winning the UEFA European Championship for Greece at Euro 2004. In total, he had 90 international appearances, ranking him 6th all-time in appearances with the Greek national team.

In 2015 he was named as manager of the Greek national under-21 football team. Until 2010, he was the President of the Panhellenic Professional Football Players Association (PSAP).
He is married to former basketball player Vaso Stasinou and they have three children. He was elected Municipal Councilor of Piraeus in the elections of 2019.