Semantic jokes involve resolving an incongruity emerging from wordplay or from a violation of world knowledge. The research has shown individuals with autism spectrum disorder (ASD) demonstrate a lower performance on humor tasks involving social situations; however, less is known about their semantic joke comprehension. This study examines 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 a multiple-choice questionnaire and time-limited computer program. Vocabulary, ToM abilities, and idiom comprehension were also tested. The results reveal that adolescents with ASD are as fast in processing semantic jokes as their age- and vocabulary-matched TD peers, but less accurate. Age and idiom comprehension significantly contributed 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 have been due to deficits in simultaneously retaining two alternative interpretations and selecting the relevant one (and not due reduced ToM abilities). Similar to the TD group, semantic joke comprehension among the ASD group appeared to be more developed with age.