Heralded as South America's answer to Picasso, Botero also tackled violence and political topics, including Colombia's internal conflicts, as well as portraying daily life.
His works have featured in exhibitions across the world.
His canvases and sculptures sell for more than $US2 million ($A3.1 million) each, according to Sotheby's.
The artist's bodacious subjects were portrayed in everyday situations - a corpulent naked woman lounging on a bed or a stout man riding a humorously out-sized horse - but served the artist's more serious goal of transporting the reader to what he called a "superlative dimension," where commonplace situations took on exaggerated proportions.
Despite the comic plumpness of many of his creations, the artist never shied away from serious subject matter - his series of paintings about the Abu Ghraib prison scandal generated discussion across the art world.
"Fernando Botero has died, the painter of our traditions and defects, the painter of our virtues. The painter of our violence and of peace," Colombian President Gustavo Petro said on X, the social network formerly known as Twitter.
Although widely known for his large subjects, Botero insisted his pieces were not focused on body type.
"I don't paint fat women," the artist told Spain's El Mundo newspaper in 2014, "no one believes me, but it's true. What I do paint are volumes".
Botero's work sometimes focused on Colombia's long-running internal conflict - he painted the aftermath of a car bomb and a group of party-goers menaced by men wielding automatic weapons and bloody machetes.
He also created tongue-in-cheek portraits of public figures, including Revolutionary Armed Forces of Colombia (FARC) rebel group founder Manuel Marulanda.
Botero also paid tribute to classic paintings with witty rehashings - his version of the Mona Lisa is notably bloated compared to Da Vinci's original.
But it was his Abu Ghraib series which commanded global attention.
The paintings, based on victim accounts and photos taken of the abuse of Iraqi prisoners by US soldiers, are explicit and harrowing.
The series was exhibited around the world, drawing tens of thousands of viewers.
The New York Times said the paintings, while not masterpieces, "restore the prisoners' dignity and humanity without diminishing their agony".
Botero's final decades as one of the world's wealthiest artists were a far cry from his humble beginnings.
Fernando Botero Angulo, the son of a travelling salesman and a seamstress, was born on April 19, 1932 in Medellin, Colombia.
As an artist, Botero sought to make his work accessible, donating more than 200 works to create the Botero Museum in Bogota, which is free and receives half a million visitors a year.
More than a hundred of the pieces were his own while others were by masters including Picasso, Dali and Monet.
He gave another 150 works to a Medellin museum and 23 of his sculptures are installed outside in the Plaza Botero.
Botero is survived by his wife Sophia Vari, two sons and a daughter.
Another son, aged four, was killed in a car crash in 1974.
Even into his eighties, the artist painted for a minimum of eight hours a day.
"I want to die painting," he told Colombia's El Tiempo newspaper the year he turned 80.
