He traveled widely in Europe (including England) with the king in the years 1548-56 but settled in Madrid when it became the home of the Spanish royal court, remaining there until his death.
He is best known for his Tientos—short, intense, liturgical and polyphonic works for keyboard music and organ.
His compositions were published in 1578, by his son Hernando de Cabezón. Many of them are still readily accessible today, in sheet music and recorded form. He produced some of the earliest extant music for solo organ.