Autism spectrum disorder (ASD) is characterized by impairments in social communication as well as restricted, repetitive behaviors. Evidence suggests that some individuals with ASD have cognitive impairments related to weak central coherence and hyperrestricted processing. Reducing noradrenergic activity may improve aspects of network processing and thus improve cognitive abilities, such as verbal problem solving, in individuals with ASD. The present pilot study explores the effects of acute administration of the beta-adrenergic antagonist propranolol on verbal problem solving in adults and adolescents with ASD. In a within-subject crossover-design, 20 participants with ASD received a single dose of propranolol or placebo on one of two sessions in a double-blinded, counterbalanced manner. Verbal problem solving was assessed via an anagram task. Baseline measurements of autonomic nervous system functioning were obtained, and anxiety was assessed at baseline and following drug administration. Participants solved the anagrams more quickly in the propranolol condition, as compared to the placebo condition, suggesting a potential cognitive benefit of this agent. Additionally, we observed a negative linear relationship between response to propranolol on the anagram task and two measures of baseline autonomic activity, as well as a positive linear relationship between drug response and baseline anxiety. These relationships propose potential markers for treatment response, as propranolol influences both autonomic functioning and anxiety. Further investigation is needed to expand on the present single-dose psychopharmacological challenge and explore the observed effects of propranolol in a serial-dose setting.