Moreno once weighed 980 pounds (444 kilograms), but lost weight after bariatric surgery in October and was even able to bathe without assistance, Sputnik reported.
"He died at 8:30 a. m. [15:30 GMT] in the ambulance, of a heart attack, while being transferred from home [in Ciudad Obregon, Sonora State] to San Jose hospital," Moreno's publicist Carmen Palacios told Univision in a Friday telephone interview.
Moreno will be buried in Mexico's Sonora State on Saturday.
Mexico was ranked as the world's most obese nation in 2013.
Before Andres Moreno Sepulveda, the world's most obese person was a Mexican man named Manuel Uribe, whose peak weight was 1,316 pounds (597 kilograms). He died at the age of 48 last year.