Introduction: Autism is a neurodevelopmental disorder that occurs in the early childhood period and is characterized by altered social interaction, communication problems, repetitive, and stereotyped behavior. Genetic, environmental, or physical risk factors are associated with prenatal, natal, or postnatal complications, leading to the development of autism spectrum disorders. Prompt diagnosis and management should be an integral component of the care provision in countries like Ethiopia. Objective: This study aimed to assess knowledge of childhood autism among nurses working in governmental hospitals in Addis Ababa, Ethiopia. Methods: Institutional based cross-sectional study design was used. The sample size was calculated using the single population proportion formula, and the final sample size was 360. Final study subjects were selected by using the simple random sampling method. Data were collected using structured self-administered questionnaires and were then coded and entered into Epi-data version 3.1 and exported to SPSS version 21 for analysis. Descriptive statistics were utilized to show frequencies and percentages, and analysis of variance was carried out to compute the association between the dependent and independent variables. Independent t-test was also done to see the association between dependent variables and independent variables with two means. A p-value of less than 0.05 was considered statistically significant. Results: The mean score for knowledge-related items was 8.79 ± 0.4. In this study, out of 331 nurses, 180 (54.35%) had good knowledge. Significant mean score difference was observed among age distribution (F-Ratio = 2.8, p-value = 0.04), level of education (F-ratio = 13.97, p < 0.001) and work experience (F-Ratio = 3.07 p-value = 0.017). Conclusion: A significant gap was observed in the overall knowledge of childhood autism among nurses employed in the governmental hospitals of Addis Ababa. The respondents’ knowledge level was significantly different among age group distributions, education levels, and work experience.