Objective To study the association of serum levels of trace elements with core symptoms in children with autism spectrum disorder (ASD). Methods From September 2018 to September 2019, an investigation was performed for 1 020 children with ASD and 1 038 healthy children matched for age and sex in the outpatient service of grade A tertiary hospitals and special education institutions in 13 cities of China. Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood Autism Rating Scale (CARS) were used to assess the core symptoms of the children with ASD. The inductively coupled plasma mass spectrometry was used to measure serum levels of trace elements magnesium, iron, copper, and zinc. Results The children with ASD had significantly lower serum levels of magnesium, copper, and zinc than the healthy children (P < 0.05). The children with severe ASD had significantly lower serum levels of magnesium and zinc than those with mild-to-moderate ASD (P < 0.05). The results of partial correlation analysis showed that serum magnesium level was negatively correlated with the total score of ABC and the score of communication (r=-0.318 and -0.282 respectively; P < 0.001), and serum zinc level was negatively correlated with the total score of ABC and the scores of communication and somatic movement (r=-0.221, -0.270, and -0.207 respectively; P < 0.001). Conclusions The serum levels of magnesium and zinc may be associated with core symptoms in children with ASD, which requires further studies. The nutritional status of trace elements should be monitored for children with ASD in clinical practice.