Diagnoses of Autism Spectrum Disorder (ASD) have rapidly increased globally. However, the lack of comprehensive epidemiological surveys and surveillance systems, able to provide official data at a national or European level is one of the main issues in the monitoring of this condition. The present study aimed to estimate the prevalence of ASD in children and adolescents aged 3–18 years old living in the province of Lecce (Southern Italy) through official data provided by the Local Health Authority of Lecce (ASL/LE) up to 31 October 2020, and compare it with school-based data concerning the number of students needing support for ASD. Based on data provided by the ASL/LE, in 2020 there were 509 cases of ASD among children and adolescents aged 3–18 years old, corresponding to a prevalence of 0.46%. A total of 408 (80.2%) were boys and 101 (19.8%) were girls. In relation to their age, 155 ASD cases (0.90%) were diagnosed in the 3–5 age group, while 222 (0.55%) in the 6–11 age group and 132 (0.25%) in the 12–18 age group. Prevalence of ASD assessed by school-based dataset was underestimated in the 3–5 age group, while the 6–11 and 12–18 age groups were consistent with the official data provided by the ASL/LE.