At the age of 18, Cuthbert won three gold medals at the 1956 Melbourne Olympics - the 100m, 200m and 4x100m relays.
Known as Australia's "golden girl", she went on to win gold in the 400m at the Tokyo Olympics eight years later.
She passed away in Western Australia on Sunday night after a long battle with multiple sclerosis.
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Australian Prime Minister Malcolm Turnbull led tributes on social media calling the runner an "inspiration and a champion on and off the track".
Friend and former Olympic sprinter Raelene Boyle said Cuthbert had won medals with "humility and distinction".
"A lot of the athletes today could take a great deal of learning out of the way she did it," Boyle told the Australian Broadcasting Corp.
Cuthbert, who was diagnosed with multiple sclerosis in 1969, was a torchbearer at the Sydney Olympic Opening Ceremony in 2000.
"Athletics Australia is saddened to confirm the passing of Olympic legend Betty Cuthbert, our thoughts with her family and friends," Athletics Australia announced on Twitter.
Cuthbert, who set nine world records during her career, was the first Australian to win triple gold.
Australian sprinting legend and four-time Olympic gold medallist Betty Cuthbert has died aged 79.