Perkins was born in Brisbane, Queensland. He attended Indooroopilly State Primary School and graduated from Brisbane Boys' College in the inner city suburb of Toowong.
He began swimming regularly at age eight as part of his rehabilitation from a serious leg injury incurred after running through a plate glass window. At age 13 his potential became obvious, and with coach John Carew guiding him he won his first medal at the Australian Championships in Melbourne in 1989, before going on to claim the silver medal in the 1500 metre freestyle at the 1990 Commonwealth Games in Auckland, New Zealand. It was here that Perkins emerged as a future star by finishing behind fellow Queenslander Glen Housman. Both Houseman (14:55.25) and Perkins (14:58.08) were the only swimmers to break 15 minutes. Fellow Australian Michael McKenzie completed the Green and Gold medal trifecta by claiming the Bronze with a time of 15:09.25. It was the first time Perkins had recorded a sub-fifteen-minute 1500 metres.
After the Commonwealth Games, Perkins' career took off. He was clear favourite to win the 1500-metre freestyle at the 1991 World Aquatics Championships in Perth, but was beaten in the final by just 0.22 seconds by German Jörg Hoffmann who set a new World Record time.
By 1992 Perkins dominated the 1500m event, lowering Hoffmann's world record with a time of 14:48.40 in Sydney. He dominated the men's 1500-metre freestyle at the 1992 Summer Olympics in Barcelona, Spain, lowering his record by 5 seconds to 14:43.48 – Housman claimed the silver with Hoffman relegated to the bronze. Perkins had also set a new world record in the 400 metre freestyle, but this was broken by Russia's Yevgeny Sadovyi in Barcelona.
At the 1994 Commonwealth Games in Victoria, British Columbia, Canada, Perkins broke the 400-, 800-, and 1500-metre freestyle world records (lowering his 1500 mark to 14:41.66). The 800-metre record was broken while swimming the 1500-metre event, meaning he broke two records in one race (the 800-metre was not actually an event at the games). The 400-metre record stood until it was broken by fellow Australian Ian Thorpe in 1999, and the 800- and 1500-metre records until 2001 when broken by Thorpe and Grant Hackett respectively. His performances in that year earned him the Male World Swimmer of the Year award from Swimming World magazine.
At the time of the 1996 Summer Olympics in Atlanta, Perkins was out of form and long-time Australian rival Daniel Kowalski was regarded as the favourite. In fact he almost failed to make the Australian team, such was his poor form. He qualified for the 1500-metre freestyle final by a mere 0.24 seconds to be the slowest of the top 8 qualifiers, and it was later revealed that before the race he felt unwell and considered not swimming. From lane eight, Perkins dominated the race being the only swimmer to go under 15 minutes (14:56.40), again relegating Kowalski, who had to fight all the way and just held off Great Britain's Graeme Smith. Despite being the world record holder, Perkins failed to qualify for the 400-metre freestyle in April, finishing third at the Australian Championships.
After his Atlanta triumph, some commentators were surprised when Perkins decided to continue competing, particularly as the rise of Grant Hackett, another Australian distance swimmer, made it seem unlikely that Perkins could win again. However, the lure of a home Olympics was too much for Perkins. Hackett completed his rise to the top by beating Perkins, who took the silver medal in a respectable time of under 15 minutes.
During the 1994 Commonwealth Games in Victoria, Canada, Perkins was nearly sent home in disgrace after he fired an air pistol inside the athletes' village. The head coach at the time wanted to send him home, but Australian team boss Arthur Tunstall intervened and he was subsequently allowed to stay.
In 2004, Perkins courted controversy when he stated that he felt the public's pressure for Craig Stevens to give up his spot in order to reinstate defending 400-metre champion Ian Thorpe to the event after being disqualified was "disgusting".
In the Australia Day Honours of 1992, Perkins was awarded the Medal of the Order of Australia (OAM). Also named an Australian Living Treasure, he was inducted into the Sport Australia Hall of Fame in 2002. In 2009 Perkins was inducted into the Queensland Sport Hall of Fame. Also in 2009 as part of the Q150 celebrations, Kieren Perkins was announced as one of the Q150 Icons of Queensland for his role as a "sports legend".
Perkins has always presented a clean-cut, well-spoken image to the public. Since his retirement, he has occasionally worked in the broadcast media and is currently head of business development and acquisitions at NAB Private Wealth. He is a current board member of Swimming Australia.
Perkins married in 1997 and has three children, Harry, Georgia and Charlie, with wife Symantha. The couple received condolences from a number of people in sports broadcasting after suffering "three miscarriages before having their third child [Charlie], and Symantha underwent radical surgery [in 2007] to combat severe migraines." Symantha has since recovered her health.
In June 2012 Perkins announced he and Symantha had separated. In a May 2014 episode of Australian Story, Perkins announced he would marry partner Karen Davis in Europe in 2014. They married in Positano, Italy in October 2014.