On 7 May 1857, the Blies Valley Railway (Bliestalbahn) was opened to neighbouring Homburg, now in the Saarland.

On 25 November 1875, the extension of the Queich Valley Railway from Annweiler was opened to traffic.

The station is located west of the city of Zweibrücken at the southwest corner of Poststraße.

The station building has lockers, vending machines and toilets; there is also a bistro and a bar.

Zweibrücken station is served each hour by Regionalbahn line 68 operated by DB Regio Südwest.