The Australian made over 250 Premier League appearances for the two English clubs from 1995 until 2008, but has most recently been playing for Melbourne Heart, who confirmed their captain would hang up his boots at the end of the A-League season.
"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."
However, the 35-year-old may be deprived of a swansong as he will miss the Heart's next two matches against Brisbane Roar and Adelaide United after suffering an abdominal strain in the defeat to the Central Coast Mariners last Sunday.
Kewell returned to his homeland last year in an effort to win a place in Australia's World Cup squad although he has missed over a third of his side's matches this season due to injury, while the Heart's position of second bottom in the table would not have aided his cause.
He can be certain of his place in history, however, having been named his country's greatest ever footballer in a vote by players, fans and journalists alike in 2012.
Sydney-born Kewell played his part in two World Cup campaigns and was one of their best players as they achieved their best-ever result in 2006, however, he was cruelly forced to miss their loss to Italy in the last-16 due to a foot infection.
He came to the fore much earlier with Leeds and was awarded the PFA's Young Player of the Year in the 1999-2000 season although he would leave the Yorkshire club in acrimonious circumstances for Premier League rivals Liverpool in 2003.
His time with the Merseysiders was blighted by injury and although he became the first Australian-born player to earn a Champions League winners' medal in 2005, Kewell was substituted midway through the first half in the final against AC Milan due to an abductor complaint.
He lasted 48 minutes in the 2006 FA Cup final triumph over West Ham before again being withdrawn due to injury, while his time in England ended two years later when he moved to Galatasaray, with whom he spent three seasons.
Kewell then moved on to Melbourne Victory in 2011 and a short spell with Qatar club Al-Gharafa followed before he came back to Australia, this time for the Victory's city rivals.
Melbourne Heart head coach John van 't Schip paid tribute to Kewell, saying: "Harry's record as a footballer speaks for itself.
"To achieve what he has done as a European player would have been amazing but to do it as an Australian player who needed to leave home as a teenager makes it a very unique and special story."
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".