Appenzeller was probably born in Oudenaarde in East Flanders, and his approximate birthdate is inferred from a document late in his life, dated July 1558, in which he gave his age as "over 70".
His several publications during the following years show that he was active then as a composer, but nothing is known of his actual whereabouts or employment until 1536, when Dowager Queen Mary of Hungary (daughter of Philip I and Joanna the Mad of Castile) brought him into her Brussels chapel as a singer.
While he spent most of this time in Brussels, he also occasionally travelled with Mary through the Habsburg lands, as it was common for the singers of the musical chapels to accompany monarchs and members of royal families.
[1] Mary moved to Spain in 1556, and at that time Appenzeller became the choirmaster at the Cathedral of St. Michael and St. Gudula in Brussels, a post he held until the end of 1558.
He also wrote elaborate canonic structures, more in the manner of the previous generation, reminiscent of the music of Josquin des Prez or Pierre de la Rue.