The singer, born blind in the Northern Territory, became the highest-selling Australian indigenous artist ever.
A former member of Yothu Yindi, his 2008 solo album sold well in several countries.
Obituary: An exquisite singer who 'spoke to the soul'
Midnight Oil frontman Peter Garrett has led tributes on social media, calling Yunupingu "a truly great musician".
"Very sad news. Too young, so much left to give. Heart goes out to family," Garrett said on Twitter.
Yunupingu's family asked media outlets not to use pictures of him after his death in accordance with indigenous traditions.
'The Australian voice of a generation'
Yunupingu's record label, Skinnyfish Music, said he was "one of the most important figures in Australian music history".
"His debut album cemented him as the Australian voice of a generation, hitting triple platinum in Australia, silver in the UK and charting in multiple other countries across the globe," the statement said.
The singer's label also praised the artist for creating opportunities for young people in the Northern Territory.
"His legacy as a musician and community leader will continue as his life's work continues its positive impact on Elcho Island, The Northern Territory, Australia and the world."
The singer had ongoing liver and kidney issues for some time, which had forced him to cancel a European tour.
The musician, who sang in English and in his native Yolngu language, performed at the Queen's Diamond Jubilee Concert in London in 2012. SHARE YOUR STORY WITH US VIA EMAIL: INFO@247NIGERIANEWSUPDATE.CO RECEIVE NEWS VIA OUR WHATSAPP, KINDLY TEXT +234 701 056 0394 TO ADD YOU CLICK HERE TO JOIN US ON OUR YOUTUBE CHANNEL FOR NEWS UPDATE CLICK HERE TO JOIN US ON TWITTER FOR INSTANT NEWS UPDATE: @247NGNEWSUPDATE CLICK HERE TO JOIN MILLIONS AROUND THE GLOBE TO READ NEWS ON OUR FACEBOOK FAN PAGE FOR INSTANT UPDATES ON INSTAGRAM CLICK HERE RECEIVE INSTANT NEWS UPDATE VIA OUR BBM BROADCAST: D3EDEFDF PLACE YOUR TEXT ADVERT BELOW:>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>