Vaca de Castro had a reputation as a man of integrity, sagacity, and courage.

He sailed from Sanlúcar de Barrameda on November 5, 1540, and arrived in Panama in January 1541.

Still on the road to Peru, in Popayán he learned of the assassination of Francisco Pizarro and the election of Diego de Almagro as governor.

Supported by Francisco de Carvajal, he defeated Almagro on September 16, 1542 in the plains of Chupas.

The New Laws caused difficulty for Vaca de Castro with Gonzalo Pizarro and other supporters of the old system.

Thereafter he concentrated his efforts on developing the country, through improving the means of communication, regulating the inns for cross-country travel, and overseeing the use of labor in the mines.

Núñez Vela had him arrested on charges of sympathizing with the rebellion of Gonzalo Pizarro.