Demetriou is the youngest son of Greek Cypriot immigrants. He has an older brother Jim Demetriou who played senior football for Essendon in the mid-1970s.
He was educated at La Trobe University, where he completed a Bachelor of Arts in 1983 and a Diploma of Education in 1984. He was awarded the University's Distinguished Alumni Award in 2009 and a Doctor of Letters (honoris causa) in 2015 in recognition of his outstanding contributions to sport management and to Australian society through his leadership and support of important social issues, and currently serves as an Adjunct Professor.
Before becoming a VFL player, he worked in the dental import industry.
Recruited from Pascoe Vale, Demetriou played for the North Melbourne Football Club as a winger between 1981 and 1987, playing 103 games and kicking 47 goals.
He had a brief move to Hawthorn in 1988, but played only three games and kicked one goal.
Between 1998 and 2000, Demetriou was CEO of the AFL Players Association.
Demetriou is best known for his position as CEO of the Australian Football League. He was elected by the board of directors at the end of the 2003 season, taking over from the outgoing CEO Wayne Jackson.
In 2008, Demetriou earned an annual salary of $1.4 million, making him the highest paid administrator or player then employed by the AFL.
In 2009, Demetriou earned $1.8 million for his role at the AFL.
In 2005 he was instrumental in securing a record breaking A$780 million TV rights deal.
In 2011, Demetriou was involved in securing a record breaking A$1.25 billion TV rights deal for the period of 2012-2016. The deal included unprecedented live TV coverage of the AFL competition in all states of Australia through free-to-air, subscription and IP television.
Demetriou has been highly influential in the AFL Commission's desire for a team to be based on the Gold Coast. North Melbourne Football Club had played three home games there in 2007 and, at the conclusion of that season, Demetriou offered the club $100 million to relocate there permanently. North Melbourne rejected that offer and, in January 2008, the AFL chairman, Mike Fitzpatrick and Demetriou announced that the Gold Coast Football Club would enter the AFL in 2011.
In 2005 Demetriou criticised the Sydney Swans and then-coach Paul Roos, labelling the team's play as "unattractive" and "ugly". He also claimed that the Swans would not win a premiership with the way they were playing, and this statement was underlined when the team suffered a 43-point defeat to St Kilda in Round 10. The defeat was the turning point in the Swans' season, with the Swans losing only two more home-and-away games for the season, both by single-figure margins and eventually winning the 2005 Premiership.
Seven years later though, Demetriou praised the Swans for their new attacking style of play under coach John Longmire and rated them as serious contenders for the premiership. Sydney won the 2012 premiership implementing a style of relentless tackling and attacking play.
Demetriou announced on 3 March 2014 that he would step down from the role as AFL CEO after eleven years, at the conclusion of the 2014 AFL season.
In April 2014, it was announced that Gillon McLachlan, Demetriou's then deputy, would be his successor. Andrew finished his tenure with the AFL in June.
Demetriou has interests in factories in Brazil and India which manufacture dental products and exports them to 70 markets, including Australia.
Demetriou has a regular spot with Red Symons on Melbourne radio station ABC 774. During the 2013 Finals Series he also co-hosted Talking Footy for the Seven Network.
Demetriou in 2014 became CEO of Acquire Learning, which was mired in controversy regarding allegations of deceptive selling practices. Acquire Learning entered voluntary administration in May 2017, shortly after Demetriou left the company.
Demetriou's first wife died in 1999. In 2002 he married his current wife Symone, and they have three daughters and a son.