This article analyses how the first circumnavigation of the world, from 1519 to 1522, introduced South America as a key space in the formation of the 'global', thus producing a historical point of inflection. We examine the commercial and political plans and networks that began to function as a result of this new connectivity, which turned the American continent into a major global axis. The analysis focuses on the way in which this voyage gave new prominence to an unexplored region of the world, namely the southernmost tip of America, thus changing the notion of habitability that had prevailed for centuries in Europe. These changes questioned the authority of 'ancient' Greek thinkers and strengthened a European historical narrative that appropriated the discovered territories and distinguished the extreme southern part of America from other southern regions, as symbolized through figures such as the Patagonian giants. I consider these changes based on evidence from Spanish sources.