Garcilaso's mother was a niece of the Sapa Inca, Huaina Capac, who died in 1525 shortly before the Spanish arrived. Huaina Capac's son by his Eldest Sister, Huascar Inca, was both son and nephew, and therefore the legitimate heir by Inca Law. Huaina Capac's son by the daughter of a Quito Chieftain, Atahualpa Inca, challenged Huascar Inca for the throne.  The Spanish arrived at a time when Atahualpa had captured Huascar, and both Prince's sought Spanish support.  Realizing that Huascar had more gold to offer the Spanish, Atahualpa quickly had Huascar murdered.

Francisco Pizarro seized the opportunity to punish Atahualpa for his crime by trying Atahualpa Inca, under Spanish Law, for the murderer of his half brother Huascar Inca. Pizarro had Atahualpa strangled to death for the crime, and took over control of the Inca Throne, assigning it to Huascar Inca's younger brother, Manco Capac. Unlike the first Manco Capac who founded the Inca Empire, this Manco Capac would rule under Spanish Authority.

Garcilaso de la Vega's father, Sebastian de la Vega y Vargas, provided him with a first rate Spanish education, while his mother's rank ensured he would get Royal Inca Instruction. He took full advantage of these opportunities and became a true scholar in his own right.