The aim of this longitudinal study was to examine changes in COVID-19 and illness-related perceptions, gastrointestinal symptoms, coping, catastrophising, psychological distress, and QoL during the COVID-19 pandemic. A total of 831 adults with a gastrointestinal condition completed an online questionnaire at baseline (May—October 2020). Of those, 270 (32.5%) participants (85.2% female, mean age = 47.3 years) provided follow-up data (March—May 2021). Repeated-measures multiple analysis of variance and a cross-lagged panel model were used to test the study hypotheses. Gastrointestinal symptoms and COVID-19 perceptions at follow-up were strongly predicted by their baseline values, while illness perceptions were predicted by baseline gastrointestinal symptoms. Cross-lagged relationships indicated a reciprocal relationship between gastrointestinal symptoms and psychological distress. Moreover, gastrointestinal symptoms had substantial predictive utility, strongly predicting future gastrointestinal symptoms, and to a lesser extent, more negative illness perceptions, greater psychological distress, and greater use of adaptive coping strategies across time.