Andres Moreno, who at his heaviest weighed 70 stone, died of a heart attack on Christmas Day
He died in Ciudad Obregón, his home city in the southern Mexican state of Sonora.
Carmen Palacios, his publicist, confirmed the news, telling Univision that he died from a heart attack at 8.30am, en route to San Jose hospital.
Ms Palacios said that he had undergone weight loss surgery in October and was doing well, having lost weight and regaining the ability to wash himself and wear trainers.
"He was really happy," she said.
Moreno was always big – when he was born, he weighed 13lbs. By the age of 10 he weighed 19 stone. Yet he was determined to lose weight this year.
José Castañeda, the surgeon who performed the weight loss surgery, said Moreno was expected to lose 58 stone, to take his weight down to 12 stone – the normal weight for a man of his 5ft 7 stature.
The surgery was difficult because the team had never operated on anyone that heavy, and were unsure whether the operating table could support his weight.
Yet it was cautiously welcomed as a success. Moreno had started walking again this month, leaning on a relative for support.
He will be buried on Saturday in Sonora.
Mexico is struggling to cope with an increasingly obese population. In 2013 the country surpassed the US to be the most obese nation in the world.
The previous record for the world's fattest man was also held by a Mexican, Manuel Uribe, from Monterrey, who weighed 88 stone. He died last year, aged 48.
The heaviest person in medical history was an American, Jon Brower Minnoch, who weighed 100 stone when he visited University Hospital, Seattle in 1976. He died in 1983, aged 42.
Britain's fattest man, Carl Thompson, died this year aged 33, weighing 65 stone. It was unclear who the "title" would now pass to.