Velasco was born in the town of Carrión de los Condes, in the province of Palencia, in 1511.

The son of a wealthy nobleman, Velasco received formal education at a young age.

On November 25, 1550, Velasco made his official entry into Mexico City, thus becoming Viceroy of New Spain.

In his final years, Velasco focused his efforts on establishing settlements in Florida, exploring the Pacific Ocean and searching for more riches for the Empire.

In 1559, Velasco sent a fleet of 13 ships under the command of Tristán de Luna y Arellano to establish settlements on the eastern coast of Florida.