Autism spectrum disorder (ASD) impacts well-being across the lifespan. Individuals with ASD evidence differences in personality traits and self-concept clarity that are predictors of well-being in typically-developing individuals. The current research replicates a growing body of evidence demonstrating differences in well-being and personality between individuals low in ASD characteristics (n = 207) and individuals high in ASD characteristics (n = 46) collected from the general population using an online survey. Results were consistent in a subsample of demographically matched pairs (n = 39 per group) and relative to norms. Further, the current research provides the first evidence that openness, conscientiousness, emotional stability, and self-concept clarity mediate the relationship between ASD characteristics and well-being.