The stream rises on the western side of the Hohneklippen crags and runs initially southwards, then swings northeast at Drei Annen Hohne.

South of Drei Annen Hohne it picks up the waters of the Wormsgraben, its main tributary.

The stream discharges into the Holtemme at Wernigerode northwest of the West Gate (Westerntor).

The Zillierbach is home to a range of rare fish species, including the protected brown trout, which features on the coat-of-arms of the town of Wernigerode as well as that of the district of Harz.

To improve the ecological environment of the Zillierbach a project was carried out from 2000 to 2002 by the German Foundation for the Environment, which envisaged five weirs with fish ladders in order to provide enable trout to negotiate the river more easily.