Dupilumab effectively treats atopic dermatitis (AD); however, its role in halting the atopic march remains uncertain.To investigate dupilumab's effect on atopic march in pediatric AD patients versus conventional immunomodulators.This retrospective cohort study utilized data from the TriNetX US Collaborative Network (2011-2024). Pediatric AD patients (≤18 years) were categorized into DUPI-cohort (newly prescribed dupilumab) or CONV-cohort (prescribed conventional immunomodulators without dupilumab). After 1:1 propensity-score matching, we analyzed atopic march progression, defined by the incident asthma or allergic rhinitis (AR). Cumulative incidence was plotted using Kaplan-Meier, with risk assessment via Cox regression.The study included 2192 patients in each cohort. The 3-year cumulative incidence of atopic march progression was lower in the DUPI-cohort than the CONV-cohort (20.09% vs 27.22%; P < .001). The DUPI-cohort demonstrated significant risk reduction in atopic march progression (hazard ratio [HR] 0.68, 95% CI 0.55-0.83), individual asthma (HR 0.60, 0.45-0.81), and individual AR (HR 0.69, 0.54-0.88). Younger patients on dupilumab exhibited a greater risk reduction for atopic march progression and individual asthma, contrasting with the opposite age-related pattern for individual AR.Observational study.Among pediatric AD patients, dupilumab was associated with reduced risk of atopic march progression compared with conventional therapies.