Juan Gracía de Loaysa (Loaísa) y Mendoza was born in 1478 in Talavera de la Reina, Spain. His parents were Pedro de Loaysa and Cathalina de Mendoza. On November 25, 1496, at the age of 18, he entered the Dominican priory of San Esteban in Salamanca. In the order were already family members from both the father's and mother's sides. From his father's family came Jerónimo de Laoysa y Carvajal, the first Archbishop of Lima and Primate of Peru. However, it seems that the provincial of the Spanish Dominicans, Alfonso de Laoysa was not part of his family. Domino Mendoza was also in the order, who had joined five years earlier.
The priory of San Esteban in Salamanca was famous for its austerity of life, which probably did not favor the novice and was the cause of constant illness. It was probably this and the influence of his older brother that brought Juan García to the priory of San Pablo in Peñafiel (Valladolid). He took his vows there in 1495. He studied at the University of Alcata and then in Valladolid. During his monastic life, he was Prior of the priory of St. Thomas of Avila, and afterwards of St. Paul in Valladolid. On April 19, 1516, at the provincial chapter in San Ildefonso de Toro, he was elected provincial of the Dominicans in Spain, and two years later - the brothers gathered at the general chapter in the monastery of Santa Maria sopra Minerva elected him master general of the order. In the Spanish rebellion of 1520-1522, he ordered not to get involved in political disputes and punished four clerics who were eventually imprisoned. In subsequent years, he visited monastic convents to pacify insurgent sentiment.
Juan was also inquisitor of Castile and Aragon and president of the Inquisition Council. Due to his activities in support of the King of Spain and Roman Emperor Charles V, he neglected his duties as a monk, so he resigned from a position of the general. On June 8, 1524, he was elected Bishop of Osma, and received the episcopal sacrament on September 29 of the same year. Emperor Charles issued an order in 1524 for bishops to reside in their dioceses, but Loaysa was not included in the order since he served as a confessor and imperial almsman. He was also Spain's ambassador to the Holy See from 1529.
On March 9, 1530, Pope Clement VII appointed him a cardinal presbyter with the titular church of St. Susanna. After being transferred to the Diocese of Sigüenza, he returned to Spain. He did not participate in the 1534 conclave and became archbishop of Seville in 1539. And after a few years he became Grand Inquisitor of Spain. He died on Maundy Thursday 1546 in Madrid.