In 1602 he was appointed second organist at the royal chapel of the Spanish viceroys; in 1614 he succeeded Trabaci as first organist when the latter became maestro di cappella on de Macque’s death.

Mayone’s two libri di diversi capricci (1603 and 1609) contain strictly contrapuntal ricercars as well as free-style toccatas and variations; together with the works of his teacher, Jean de Macque and his co-student G. M. Trabaci, these compositions are perhaps the closest ancestors of Frescobaldi’s keyboard works.

Mayone recognized the novelty of his own music; in his preface of 1609 he wrote:
“Let him not be scandalized and adjudge me little observant of the rules of counterpoint. Whenever compositions are adorned with passage-work there will occur some false notes that pass contrary to the contrapuntal laws; but without them it is impossible to make a beautiful effect.”

Mayone’s most original compositions are his toccatas. In the book of 1609 we find two toccatas composed for a cimbalo cromatico - the earliest known works composed for this instrument. Several pieces are furthermore specifically composed for the harp.