Background: Symptoms caused by chronic pancreatitis (CP) are common but often elusive hampering therapeutic decisions. Though correlations of morphologic findings in imaging and clinical appearance remain vague. We aimed in investigating whether a distinct combination of clinical parameters can better define the extent of pancreatic insufficiency and disease burden. Methods: Data from 350 CP patients were evaluated retrospectively from a single center data base following predefined criteria: (i) confirmed CP, (ii) endoscopic ultrasound (EUS) plus (iii) fecal elastase-1 testing, (iv) age ≥18 years, and (v) Cambridge Score ≥1 on EUS evaluation. Results: In total, 182 patients (137 male, 45 female) fulfilled criteria. Median age was 52 years (range 19–88 years). Etiology distributed as follows: idiopathic 50%, alcohol 42.3%, autoimmune 7.7%. Totally, 56.6% of patients suffered from chronic pain that was significantly associated with male sex and younger age. Stool elastase-1 activity discriminated exocrine pancreatic function in Cambridge IV significantly better than in lower stages. Similarly, the endocrine function was significantly more reduced in Cambridge IV CP. Multinominal regression analysis revealed (i) presence of diabetes, (ii) presence of complications, and (iii) extent of Cambridge score as main determinants for exocrine impairment. Conclusion: A high disease burden is linked to extensive morphological alterations in EUS, while pain is more frequent in younger and male patients. The etiology of CP predicts the course of disease in terms of complications.