The 35-year-old, who is currently captain of Melbourne Heart in his native Australia, made over 250 Premier League appearances for the two clubs between 1995 and 2008.
Kewell also won over 50 caps for Australia, who he represented at the 2006 and 2010 World Cups.
"On behalf of Harry Kewell, Melbourne Heart FC confirms the Socceroo legend will retire from professional football at the end of the current Hyundai A-League season," said a statement on the club's website.
"Kewell's final appearance for Melbourne Heart FC will be against the Western Sydney Wanderers at AAMI Park in the final round of the Hyundai A-League 2013/14 season on Saturday 12 April."
Kewell himself said on Twitter: "On my way to officially announce my retirement. Thank you for all the kind tweets you've sent so far. #EndofanEra".
Kewell came through the Leeds youth ranks and established himself as one of their best performers in the Premier League under George Graham and then David O'Leary.
He was awarded the PFA's Young Player of the Year in the 1999-2000 season but left the Yorkshire club in acrimonious circumstances four years later to join Liverpool, with whom he won the Champions League in 2005 and FA Cup in 2006, despite being substituted in the finals of both competitions because of injury.
He spent three seasons with Turkish side Galatasaray and had short spells with Melbourne Victory and Qatar club Al-Gharafa before returning to Australia, this time for the Victory's city rivals.
Kewell is guaranteed his place in Australian football history, having been named his country's greatest ever footballer in a vote by players, fans and journalists alike in 2012.