Andre Roussimoff was born in Moliens, the son of Boris and Mariann Roussimoff. His parents were of Bulgarian and Polish descent. His nickname growing up was "Dede". As a child, he displayed symptoms of his gigantism very early, reaching a height of 191 cm (6 ft 3 in) and a weight of 94 kg (208 lb) by the age of 12.

At the age of 17, Roussimoff moved to Paris and was taught professional wrestling by a local promoter who recognised the earning potential of Roussimoff's size. He trained at night and worked as a mover during the day to pay living expenses. Roussimoff was billed as "Geant Ferre", a name based on the French folk hero Grand Ferre, and began wrestling in Paris and nearby areas. Canadian promoter and wrestler Frank Valois met Roussimoff in 1966, becoming his business manager and adviser. Roussimoff began making a name for himself wrestling in the United Kingdom, Germany, Australia, New Zealand, and Africa.  He made his Japanese debut in 1970, billed as "Monster Roussimoff", wrestling for the International Wrestling Enterprise. Wrestling as both a singles and tag-team competitor, he quickly was made the company's tag-team champion alongside Michael Nador. During his time in Japan, doctors first informed Roussimoff that he suffered from acromegaly.  Roussimoff next moved to Montreal, Canada, where he became an immediate success, regularly selling out the Montreal Forum. However, promoters eventually ran out of plausible opponents for him and, as the novelty of his size wore off, the gate receipts dwindled. Roussimoff was defeated by Adnan Al-Kaissie in Baghdad in 1971, and wrestled numerous times in 1972 for Verne Gagne's American Wrestling Association (AWA) as a special attraction until Valois appealed to Vince McMahon Sr., founder of the World Wide Wrestling Federation (WWWF), for advice. McMahon suggested several changes. He felt Roussimoff should be portrayed as a large, immovable monster, and to enhance the perception of his size, McMahon discouraged Roussimoff from performing maneuvers such as dropkicks (although he was capable of performing such agile maneuvers before his health deteriorated in later life). He also began billing Roussimoff as "Andre the Giant" and set up a travel-intensive schedule, lending him to wrestling associations around the world, to keep him from becoming overexposed in any area. Promoters had to guarantee Roussimoff a certain amount of money as well as pay McMahon's WWWF booking fee.

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