He studied at the University of Heidelberg. Travelling from university back to his home town in 1482, he was surprised by a snowstorm and took refuge in the Benedictine abbey of Sponheim near Bad Kreuznach. He decided to stay and was elected abbot in 1483, at the age of twenty-one. He set out to transform the abbey from a poor, undisciplined and ruinous place into a centre of learning. In his time, the abbey library increased from around fifty items to more than two thousand. However, his efforts did not only meet with praise, and his reputation as a magician did not further his acceptance. Increasing differences with the convent led to his resignation in 1506, when he decided to take up the offer of the Lord Bishop of Würzburg, Lorenz von Bibra (bishop from 1495 to 1519), to become abbot of the Schottenkloster in Würzburg. He remained there until the end of his life.
His most famous work is Steganographia (written c.1499; published Frankfurt, 1606), a work superficially on cryptography, but containing a hidden treatise on black magic; this work lent its name to the modern field of steganography.
Other works include De septum secundeis (The Seven Secondary Intelligences, 1508), a history of the world based on astrology; Annales Hirsaugiensis (1514); and Polygraphia (1518).
Among his pupils was Heinrich Cornelius Agrippa (1486-1535).