The Australian sprinter was once the holder of both the 50-metre and 100m freestyle world records, and was a three-time medallist at the 2008 Olympic Games in Beijing.
Sullivan, 28, was once the poster boy of Australian swimming, combined with former partner Stephanie Rice, however he has called time on his career less than a week out from the Commonwealth Games - at which he has been a three-time gold medallist - in Glasgow.
"One of the things I'm most proud of throughout my career is overcoming injuries. I'm at a point where I've had one too many injuries, and it has become too much to manage," Sullivan said via a statement.
"In the end my body has let me down, so I'm very disappointed, but it's the right time.
"I'm very excited about the direction that Swimming Australia is heading with (coaches) Jacco Verhaeren and Michael Scott at the helm.
"We have an exciting young team heading to the Commonwealth Games, who we should all be getting behind."
At his peak, Sullivan won two silver medals in Beijing - pipped for gold in the 100m freestyle by 0.11 seconds by France's Alain Bernard, after setting the world record in the semi-finals.
Sullivan was also a part of the Australian 4x100m medley team that claimed second, while he also snared bronze in the 4x100m freestyle relay.
Former team-mate and two-time Olympic gold medallist Michael Klim hailed Sullivan's toughness to continually battle fitness and still perform on the world stage.
"It was an absolute pleasure to have trained and competed alongside and against Eamon during his many successful years on the Australian swimming team," Klim said.
"Even though this career was sometimes plagued with injuries, he always found it in himself through sheer determination to perform to the best of his ability, which made him one of the toughest and best sprinters Australia has ever seen.
"He has left a great mark on the sport which will be remembered forever."