He was choirmaster of Ely Cathedral from about 1543 and also organist there from 1559. The title page to Tye's Actes of the Apostles (London 1553) describes him as one of the Gentlemen of his grace's most honourable chapel, and he may have been music teacher to King Edward VI, who reportedly quoted his father, Henry VIII, as saying England hath one God, one truth, one doctor hath for music's art, and that is Doctor Tye, admired for skill in music's harmony.
Tye remained at Ely under the reign of the Catholic Queen Mary despite his apparent Protestant leanings. In 1560 or 1561 he resigned his post at Ely and took holy orders, becoming Rector of Doddington, Cambridgeshire. He died in 1572 or 1573, apparently still active under Elizabeth, for Anthony Wood relates that
Dr Tye was a peevish and humoursome man, especially in his latter dayes, and sometimes playing on ye Organ in ye chap. of qu. Elizab. wh. contained much musick, but little of delight to the ear, she would send ye verger to tell him yt he play'd out of Tune: whereupon he sent word yt her ears were out of Tune.
Tye's Latin church music includes masses (notably one based on the song "The Western Wynde", also the basis of masses by John Taverner and John Sheppard) and psalm settings. He also composed works in English for the Church of England, including services and anthems, and pieces for consorts of viols, including over twenty In Nomines.