Speeding in a work zone needs to be tackled effectively to enhance work zone safety. This study evaluates the influence of three different work zone signs—speed photo enforced signs, dynamic speed display signs and reduced speed limit signs—on driver speeding behavior using a medium-fidelity driving simulator. The speed photo enforced and reduced speed limit signs were placed at intervals before the start of the work zone and in the work zone. A virtual work zone network was built to replicate the Baltimore–Washington Parkway (MD-295). A total of 66 participants from different socioeconomic backgrounds participated in 264 driving simulation sessions. The speeds were measured over four phases: initial speed area, sign visible area, sign readable area and post sign area. An analysis of variance and post hoc analysis showed that the speed photo enforced sign was the most effective of the three signs. The second speed photo enforced sign within the work zone was more effective at reducing speed than the sign before the start of the work zone, especially in the post sign area. It was observed that female participants tend to slow down more when encountering a speed photo enforcement sign.