Summary Background We developed a non‐invasive bowel ultrasound score (BUSS) to assess disease activity in Crohn’s disease (CD). BUSS >3.52 is an indicator of endoscopic activity (SES‐CD>2). Aim To assess whether BUSS, in addition to detecting inflammatory lesions, also detects relevant changes of these lesions over time. Methods This was a prospective observational study of 49 patients with active CD. All patients underwent bowel ultrasound and colonoscopy at baseline and at re‐assessment after treatment with biologics and/or immunosuppressants. The primary objective was to assess the sensitivity to change of BUSS in patients treated for active CD, using the SES‐CD as reference standard. Results BUSS changed significantly from baseline to re‐assessment in patients achieving endoscopic response (a reduction of SES‐CD of at least 50% vs baseline: 4.87 [3.78‐6.0] vs 2.47 [2.25‐3.36], P < 0.001) and endoscopic remission (SES‐CD ≤ 2: 4.65 [3.58‐6.03] vs 2.25 [2.25‐3.46], P = 0.003). A change of −1.2 in BUSS over time predicted endoscopic response (AUC 0.786, 95% CI 0.645‐0.890; sensitivity 74%, specificity 83%). BUSS determined endoscopic response with 80% accuracy, and endoscopic remission with 78% accuracy. BUSS accurately detected changes in lesion severity (Guyatt score: 1.41 and standardized effect score: 1.74). BUSS did not change significantly in patients who did not achieve endoscopic response (5.62 [5.26‐6.15] vs 5.70 [4.97‐6.19], P = 0.53) or endoscopic remission (5.62 [5.18‐6.14] vs 5.10 [4.58‐6.05]; P = 0.10). Conclusion BUSS is sensitive to change in CD.