Autistic individuals are at particular risk of experiencing mental health problems during the COVID-19 pandemic, yet little is known about personal characteristics that may underlie this vulnerability. This longitudinal questionnaire study with 149 autistic and 147 non-autistic adults investigated the association between perceived stress and anxiety and depressive symptoms, measured 4 months later. In addition, the moderating impact of intolerance of uncertainty and coping styles on this association was examined. Confirming previous studies, autistic adults reported poorer mental health than non-autistic individuals. Results demonstrated similar moderation models across individuals with versus without autism. Perceived stress at timepoint 1 was associated with anxiety and depression at timepoint 2. Across both participant groups, individuals with maladaptive coping strategies and higher levels of intolerance of uncertainty at timepoint 1 showed more internalizing symptoms at timepoint 2. The findings demonstrate the burden of the pandemic on the mental health of autistic adults, especially on those with high levels of perceived stress, maladaptive coping strategies, or intolerance of uncertainty. Interventions to support autistic adults during and after the pandemic might involve providing psychoeducation about the impact of stress, coping, and intolerance of uncertainty on internalizing symptoms, and teaching more adaptive ways to cope with difficult circumstances.