Many youth with autism spectrum disorder (ASD) experience co-occurring conditions, such as gastrointestinal (GI) problems and internalizing symptoms. However, the relationship among these co-occurring problems is not well-understood. We analyzed parent reports of GI problems and internalizing symptoms of 621 youth with ASD using path models in a structural equation modeling framework. The best-fitting model was a bidirectional model wherein internalizing symptoms, including withdrawn and anxious behavior, were correlated with GI problems, including constipation, diarrhea, nausea, and stomach pain. This study provides a better understanding of the relationship among co-occurring conditions in youth with ASD and should encourage clinicians to consider treatment of underlying internalizing symptoms or GI problems when providing services for individuals with ASD.