Objectives: In patients with chronic pancreatitis (CP), the aim was to explore the association between pancreatic morphological progression over four years and corresponding changes in disease characteristics, including quality of life (QOL), pain, and exocrine pancreatic function. Methods: Twenty-five patients with CP were followed by magnetic resonance imaging (MRI). Data were obtained at baseline and after 4-year follow-up, including clinical information, QOL, and pain as assessed by validated questionnaires. Morphological assessments were derived from the same MRI scanner and included pancreatic gland volume, apparent diffusion coefficient values, fat signal fraction, and main pancreatic duct diameter. Results: After four years, CP patients showed significant progression in morphological parameters of the pancreas, except for the ductal-related changes (p < .13). Hence, patients developed reduced pancreatic volume by 13.5% (p < .001), an increase of fibrosis by 10.8% (p < .001), and an increase of fat infiltration by 7.6% (p < .001). In contrast, the patient-reported outcomes of QOL and pain did not change significantly over four years (all p > .05). Moreover, the progression of morphological imaging findings was not related to changes in QOL, pain severity, and pain interference (all p > .05). There was, however, an association between the 4-year progression of pancreatic atrophy and the decrease in fecal elastase concentration (r = 0.61; p < .001). Conclusions: Progression of gland morphology in CP did not correlate with changes in the quality of life or pain symptoms. Advanced pancreatic imaging techniques may be a highly sensitive tool for monitoring morphological disease progression, but do not directly reflect patients' disease burden.