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Impaired language and communication are commonly observed in youths with autism spectrum disorders (ASDs). However, the organization of semantic knowledge in youths with ASD remains unclear compared to typically developing (TD) youths. The present study addresses this issue by using functional magnetic resonance imaging (fMRI) to examine the distinction between association strength and categorical relatedness of semantic knowledge. A sample of 31 male youths with ASD (mean age = 12.1 years, SD = 1.2) and 38 TD youths (mean age = 11.9 years, SD = 1.0) was recruited with matched age, gender, and handedness. Participants decided if two visually presented Chinese characters were semantically related during fMRI scanning. For weaker association strength, the ASD group showed greater left cuneus activation, which was positively correlated with the picture completion for visual perception, whereas the TD group showed greater middle temporal gyrus and inferior frontal gyrus activation. For higher categorical relatedness, the TD group showed greater activation than the ASD group in the occipitotemporal cortex and left precuneus, which was positively correlated with the similarities for concept formulation. Findings imply that the ASD group may use lower‐level visual information for both association strength and categorical relatedness. The TD group showed higher‐level controlled processes of more elaborate semantic representations for association strength and more elaborate features of categorical knowledge for semantic selection and integration. Autism Res 2019, 12: 1484–1494. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryIndividuals with autism spectrum disorder (ASD) often present language/communication impairments. Exploring the difference of semantic processing between youths with ASD and typically developing (TD) youths is crucial for understanding the organization of semantic knowledge. We found different neural substrates of semantic knowledge between these two groups. ASD youths may rely more on lower‐level visual information during semantic judgments, whereas TD youths showed higher‐level controlled processes of more elaborate semantic representations for selection and integration of words, phrases, and sentences.