Prevalence rates of depression are higher in autistic youth than neurotypical peers, yet the effects of autism spectrum disorder diagnosis and sex on depressive symptom severity remain incompletely understood, particularly in specific age groups. Using the Children's Depression Inventory, Second Edition, this study explored diagnostic- and sex-based differences in depressive symptom severity in a sample of 212 autistic and neurotypical early adolescents (10:0-13:5 years). Significant group differences were found according to autism spectrum disorder diagnosis [d = 0.587, 95% confidence interval (0.308, 0.867)] and sex [d = 0.365, 95% confidence interval (0.089, 0.641)], with more depressive symptoms endorsed in the autism spectrum disorder and female groups. However, the interaction of diagnosis and sex was not significant, suggesting an additive risk of autism spectrum disorder status and female sex. Item-level analyses showed diagnostic differences on nearly half of the CDI-2 items with higher severity in the autism spectrum disorder group (Probability of Superiority range = 0.42-0.65), differences within the sexes, and differences by diagnosis, which persisted when limiting analyses to children with high levels of depressive symptoms. A more nuanced understanding of symptom endorsement and the roles of diagnosis and sex may uncover salient intervention targets for depression in the unique context of autism spectrum disorder.