More than 800,000 students with autism spectrum disorder (ASD) are served in U.S. public schools, a number that has increased annually for almost 20 years since Individuals with Disabilities Education Act (IDEA) included ASD as an eligibility category. These students often experience widespread and persistent reading comprehension challenges. A systematic review and meta-analysis, anchored in a construction-integration model of reading comprehension, was undertaken to examine single-subject research design (SSRD) and group design studies aimed at remediating reading comprehension challenges in students with ASD. Reading comprehension instruction was operationalized by surface, textbase, and situation model levels. Random effect modeling with robust standard error estimations suggested small yet statistically significant intervention effects. Situation model-level interventions demonstrated the highest intervention effects in group design studies. Across designs, retelling and curriculum-based question-answering measures demonstrated larger effect sizes than cloze and norm-referenced measures. Methodological quality analysis suggested that few individual SSRD and group studies had high design quality with large intervention effects. We concluded that reading comprehension instruction focused on the situation model level should be prioritized for students with ASD, and future studies should reduce bias in designing intervention studies.A utism spectrum disorder (ASD) is characterized by significant challenges with communication, behavior, and social skills, as well as frequent learning challenges (American Psychological Association, 2017). One in 160 school-aged children worldwide is diagnosed with ASD (World Health Organization, 2019), and U.S. public schools currently serve more than 800,000 students with ASD (US Department of Education, 2022). With the passage of the Every Student Succeeds Act (, 2015), special education and general education teachers are required to operate from the premise that all students can succeed academically and to use evidence-based practices to achieve this end (Chenoweth, 2016). An ongoing challenge in meeting this legal mandate for students with ASD has been the learning differences and persistent reading comprehension challenges of students with ASD (American Psychological Association, 2017; CDC, 2020) within the context of one-size-fits-all instructional approaches lacking differentiation (Bondie et al., 2019).