Objectives: To analyze serial changes in body composition and investigate the association between body composition changes and disease activity changes in patients with Crohn’s disease (CD). Methods: Seventy-one patients with CD who had been treated and followed-up at our institution were included. Two to four computed tomography images were acquired at baseline, and the 2–5-year, 5–8-year, and last follow-ups were selected per patient for body composition and disease activity analyses. Visceral fat area (VFA), skeletal muscle index (SMI; skeletal muscle area/height2), and subcutaneous fat area (SFA) were assessed using an artificial-intelligence-driven fully automated method. Disease activity was assessed using a modified computed tomography scoring system and the Simple Endoscopic Score for Crohn’s Disease. The associations between body composition, disease activity, and remission were investigated. Results: The mean age was 29.83 ± 11.27 years; most patients were men (48/71, 67.6%); and the median follow-up was 144 (12–264) months. Overall, VFA and SFA gradually increased, while SMI decreased during the follow-up. Sarcopenia was associated with the female sex, higher disease activities at baseline (p = 0.01) and the last follow-up (p = 0.001). SMI and SFA inversely correlated with the disease activity, i.e., the more severe the disease activity, the lower the SMI and SFA (p < 0.05). SMI at the last follow-up was the only significant predictor of remission (OR = 1.21, 95% confidence interval: 1.03–1.42, p = 0.021). Conclusion: SMI decreased while VFA and SFA increased during the treatment follow-up in patients with CD. Sarcopenia was associated with higher disease activity, and SMI and SFA inversely correlated with disease activity. SMI at the last follow-up was the significant factor for remission.