Endometriosis and irritable bowel syndrome (IBS) share common pathophysiological and risk factors, often leading to misdiagnosis, diagnostic delays, and treatment implications. Further, both conditions are associated with biopsychosocial comorbidities, resulting in compromised wellbeing and reduced health-related quality of life (HRQoL). This longitudinal prospective study consisting of 610 adult women with endometriosis (EndoOnly; n = 352), and with endometriosis and co-occurring IBS-type symptoms (Endo + IBS; n = 258) aimed to investigate the differences in biopsychosocial factors, specifically HRQoL, psychological distress, pain, fatigue and menstrual symptoms over a three-year period. Using linear mixed models, results demonstrated that individuals with Endo + IBS were more likely to experience lower HRQoL and higher functional pain disability, fatigue, and menstrual symptoms compared to individuals with EndoOnly over three years. Results showed significant linear declines in rumination, total pain catastrophising, pain severity and helplessness for both groups; however, the rate of change for the Endo + IBS group tended to diminish and change direction over time. Further individuals with Endo + IBS were inclined to exhibit more complex change trajectories in psychological distress, magnification, and fatigue over time, with a trend towards worse outcomes overall. The onset of the COVID-19 during the study appeared to produce unexpected and inconsistent patterns of change for both groups. Findings highlight important implications for the implementation of multidisciplinary psychosocial healthcare, to help improve diagnosis, clinical management and overall health outcomes for individuals living with endometriosis and co-occurring IBS-type symptoms.