Semantic jokes involve resolving an incongruity emerging from wordplay or from violation of world knowledge. Research has shown individuals with autism spectrum disorder (ASD) demonstrate lower performance on humor tasks involving social situations, but less is known about their semantic joke comprehension. This study examined semantic joke comprehension among adolescents with ASD, and its possible relationship to vocabulary size, theory of mind (ToM), and idiom comprehension. Thirty-two adolescents with ASD and 32 typically developed (TD) peers participated. Semantic joke comprehension was assessed via multiple-choice questionnaire and time-limited computer program. Vocabulary, ToM abilities, and idiom comprehension were also tested. Results revealed that adolescents with ASD were as fast in processing semantic jokes as their age- and vocabulary-matched TD peers but less accurate. Age and idiom comprehension contributed significantly to semantic joke comprehension among both groups. As semantic joke comprehension is based on incongruity resolution, the greater difficulties in comprehension among the adolescents with ASD may be due to deficits in simultaneously retaining two alternative interpretations and selecting the relevant one. Like the TD group, semantic joke comprehension among the ASD group appeared more developed with age. Future neuroimaging studies should test semantic brain region involvement in semantic joke comprehension in ASD.