Purpose: The objective of this study was to investigate the behavioral changes in the core features and challenging behaviors of children with Autism Spectrum Disorder (ASD) during the COVID-19 Omicron wave (from December 2022 to January 2023) in China. Patients and Methods: A total of 515 caregivers of children with ASD completed an online survey. This survey was designed to assess the sociodemographic characteristics of the children and their caregivers, the clinical features of COVID-19, the manifestation of core ASD features and challenging behaviors, and the alterations in daily life following the COVID-19 Omicron variant wave. Results: The children with ASD had an average age of 5.4 years, with 79.6% being male. After the Omicron wave, the proportions of participants with worsening core ASD features and challenging behaviors were 22.9% and 37.1%, respectively. Sleep disorders (20.0%), eating problems (18.6%), and inattentive symptoms (17.5%) were the most frequently reported worsening behaviors. The factors associated with the worsening of core ASD features included infection with the Omicron variant of COVID-19, reduced outdoor activity, and a lower score of caregiver health-related quality of life (HRQoL). The worsening of challenging behaviors was associated with infection with the Omicron variant of COVID-19, a lower frequency of rehabilitation training, and a lower score of HRQoL. Conclusion: The outbreak of the COVID-19 Omicron variant had an impact on the behaviors of autistic children. The behavior changes in core ASD features and challenging behaviors differed and were associated with COVID-19 infection and other factors.