Background: The phenomenon whereby behavior becomes controlled by one aspect of the environment at the expense of other equally-salient aspects of the environment (stimulus over-selectivity) is extremely common in many with Autism Spectrum Disorder (ASD). However, the theoretical mechanisms underpinning over-selectivity and its remediation are not well understood. Four experiments explored whether principles derived from associability accounts of learning, notably the concept of uncertainty, might allow better theoretical understanding of the phenomenon. Method: Participants with ASD who had language impairments received simultaneous discrimination training (AB+/CD-), and were tested in extinction regarding the degree to which the separate elements (A and B) of the previously reinforced compound (AB+) controlled behavior. Results: All experiments established the presence of over-selectivity; choosing one stimulus element to a greater-extent than the other. In Experiments 1 and 2, relative to a 100% feedback schedule, over-selectivity reduced when a 50%, but not a 25%, schedule of feedback was used. In Experiment 3, prolonged schedule exposure reduced over-selectivity. In Experiment 4, change from a 100% to a 33% schedule did not reduce over-selectivity. Conclusions: These results suggest that unpredictability, rather than variability per se, or reinforcement reduction and change, reduces over-selectivity. This suggests that attentional mechanisms, especially uncertainty, may play a role in this phenomenon during its acquisition and remediation.