Manuel Uribe's death was confirmed by a health department official from Nuevo Leon, the state where he lived.
According to the official, who could not be named, Mr Uribe was taken to hospital on Friday 2 May with an abnormal heartbeat.
He had to be taken there by emergency and civil defence workers using a crane.
Mr Uribe's cause of death has yet to be determined.
As well as the problems with his heart, he was also thought to have had problems with his liver.
He was named a Guinness World Record holder in 2006 after his weight was recorded at 1,230lb (560kg).
He had slimmed down to 867lb (394kg) since then.
Mr Uribe lived in the Mexican city of Monterrey, close to Mexico's border with the US, and had been stuck in bed for many years as he could not walk by himself.
Since 2002 he had relied on his mother and friends to feed and clean him.
He married Claudia Solis in 2008 and left his home for the wedding, one of the few times he was able to do so in recent years.
Mr Uribe said he weighed more than 20 stone (115kg) as a teenager and that from 1992 his weight began to increase.
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