Florencio was born in Buenos Aires on 23 February 1808, he was the sixth child of Don Jacobo Adrián Varela and María de la Encarnación Sanjinés, he had a keen interest in the literary arts from a young age.

After graduating from the University of Buenos Aires in 1827 Varela became involved in politics, his association with the Partido Unitario meant that he was exiled to Montevideo in Uruguay after the defeat of General Juan Lavalle.

Varela settled in Montevideo starting a family and associating with several other exile writers and intellectuals who opposed the rule of Governor Juan Manuel de Rosas.

After suffering a heart condition Varela moved to Rio de Janeiro in Brazil where he recovered his health and worked on his history of Argentina.

In 1843 he travelled to Europe in order to garner British and French support to the project of a new state comprising Uruguay, Rio Grande do Sul and some Argentine provinces.