We conducted a cluster-randomized trial to assess the impact of a school-based water treatment, hygiene, and sanitation program on reducing infection with soil-transmitted helminths (STHs) after school-based deworming. We assessed infection with STHs at baseline and then at two follow-up rounds 8 and 10 months after deworming. Forty government primary schools in Nyanza Province, Kenya were randomly selected and assigned to intervention or control arms. The intervention reduced reinfection prevalence (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.31-1.00) and egg count (rate ratio [RR] 0.34, CI 0.15-0.75) of Ascaris lumbricoides. We found no evidence of significant intervention effects on the overall prevalence and intensity of Trichuris trichiura, hookworm, or Schistosoma mansoni reinfection. Provision of school-based sanitation, water quality, and hygiene improvements may reduce reinfection of STHs after school-based deworming, but the magnitude of the effects may be sex- and helminth species-specific.