Gomarus served as pastor of a Dutch Reformed church in Frankfurt am Main from 1587 until 1593, when the congregation was dispersed by anti-Protestant persecution. In 1594 he was appointed professor of theology at the University of Leiden, where he became a leader of the opponents of Arminius. When Arminius joined the faculty in 1603, their disputes increased in intensity.

Gomarus debated Arminius before the assembly of the estates (regional governmental bodies) of Holland in 1608, and he and four followers debated five Arminians (also known as the Remonstrants) in the assembly in 1609. In their disputes, Gomarus upheld the strict Calvinist view that those elected to salvation had already been chosen before Adam's Fall, but Arminius allowed for the possibility that every individual was potentially among the elect. Later a professor at Saumur (France) and at Groningen, Gomarus took a leading part in the Synod of Dort (Dort, Synod of) (Dordrecht) in 1618–19 as an opponent of Arminianism, which was condemned at the synod.