The increased prevalence of autism spectrum disorder (ASD) has placed a significant emotional and psychological burden on mothers. We explored the association between the severity of ASD symptoms in children and the mental health of their mothers during the COVID-19 pandemic. Our study included 1,924 mothers of children with ASD, enrolled in a web-based cross-sectional survey over 85 consecutive days to gather clinical and sociodemographic data. The severity of ASD symptoms was obtained according to the children’s age. Using the Depression, Anxiety, and Stress Scales (DASS-21) scale, we found that 35.8 percent of mothers experienced both anxiety and depression. A high education level and a high family income reduced the chance of concurrent anxiety and depression. Conversely, unemployment, a child using psychiatric medication, and higher severity of ASD symptoms increased the chance. Notably, the severity of the ASD symptom was the sole predictor of maternal co-occurring anxiety and depression across all age groups (<3 years aOR = 2.04, 95%CI 1.07-3.89; 3-5 years aOR = 2.76, 95%CI 1.67-4.56; ≥ 6 years aOR = 1.61, 95%CI 1.04-2.50). Recognizing the challenges associated with ASD leads to greater acceptance and tailored interventions, ultimately improving the overall well-being of both individuals with ASD and their mothers.