Saint Anthony the Abbot, already an old man, is shown meditating near the trunk of a dry tree. Both it, the water in the foreground, and the lush vegetation in the background are supposed to represent the desert in which the saint spent twenty years alone. At that time, a desert was not a place without life, but rather one characterized by solitude. Here, it is inhabited by demons intent on tempting Saint Anthony. Bosch includes them in this work, almost like the saint's identifying attributes, along with the customary ones: the saint's dark brown habit with the Greek letter, “tau,” and the pig by his side.

Originally framed with a semi-circular arch, this mature work is by the painter's own hand and of great technical quality, though difficult to date with exactitude.

Felipe II sent it to the Monastery of El Escorial, from whence it entered the Prado Museum.