Matthys was born in Haarlem, in the Holy Roman Empire's County of Holland, where he worked as a baker, and was converted to Anabaptism through the ministry of Melchior Hoffman in the 1520s.
Matthys rejected the pacifism and non-violence theology of Hoffman, adopting a view that oppression must be met with resistance.
Matthys identified Münster as the "New Jerusalem", and on January 5, 1534, a number of his disciples entered the city and introduced adult baptism.
They declared war on Franz von Waldeck, its expelled prince-bishop, who besieged the fortified town of Münster.
In April 1534, on Easter Sunday, Matthys, who had prophesied that God's judgment on the wicked would take place on that day, attacked with twelve followers, under the idea that he was a second Gideon, and was cut off with his entire band.