Anxiety is a common co-occurring condition for autistic preschoolers. Whilst there has been extensive research evaluating anxiety prevention/reduction interventions for neurotypical preschoolers, such research is limited for autistic children. Fifty-seven parents of autistic 4–5-year olds, with varying levels of anxiety, participated in a randomised controlled trial of an autism-specific, parent-mediated intervention (CLK-CUES) to prevent or reduce anxiety in autistic preschoolers. Baseline, short-term (post-intervention) and longer term (12 months follow-up) assessments included child anxiety (ASC-ASD-P and PAS-R), intolerance of uncertainty, and parent well-being. (Trial registration ACTRN12620001322921). There were no reports of harmful effects of the intervention or trial. Linear mixed models show a significant group x time interaction for ASC-ASD-P Total score and the Uncertainty subscale with medium and large effect sizes. Post-hoc analyses show a significant decline for only the intervention group in anxiety (specifically, anxiety around uncertainty) from pre-post intervention, maintained at one year follow-up. There was no change on the PAS-R or other ASC-ASD-P subscales. CLK-CUES shows promise as a way to prevent and reduce anxiety in young autistic children, specifically anxiety related to uncertainty. Trials with larger samples are warranted. Findings also highlight the importance of using measures designed for autistic children.