The Monastery of San Antonio el Real was founded by king of Castile, Henry IV (Enrique IV) when Pope Calixto III granted him a papal bull giving him permission to do so on the 19th of May, 1455. In exchange, the king authorised Franciscan monks to take up residence in the Prince's Lodge, some remains of which may still be seen behind the side façade giving access to the enclosed monastery.
By the time the church was completed, the altarpiece had already been installed in the chancel. In 1466, when Baron León de Romisthal visited the city of Segovia, he described it as: "a beautiful altarpiece decorated with gold and silver". According to his statement, the king himself was the person who had paid the cost of the work, since he also added in the chronicle dealing with his visit that "according to popular rumour, the king himself paid for the temple and its adornments: some 12,000 aúreos (gold coins of the period)". The king apparently became involved in the project when he conceived the monastery as being his final resting place. According to the Clarisse nuns when they took up residence here in 1488, thus converting the Monastery into a Convent, they were very surprised indeed by the magnificence of the temple's main chapel.