Bottle-fed infants are at greater risk for overfeeding and rapid weight gain (RWG); evidence-based strategies for promoting healthy bottle-feeding practices are needed. Our aim was to assess whether policy, systems, and environmental (PSE) strategies for promoting responsive bottle-feeding practices within the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) were associated with lower risk for RWG. We conducted a matched-pair cluster randomized trial. PSE strategies were implemented at 3 WIC clinics in Los Angeles County. PSE clinics were compared with 3 matched control clinics. Mothers and infants were assessed when infants were newborn and 3 months and 6 months of age. Participants were mothers (n = 246) who enrolled their newborn infants (younger than 60 days) into WIC between May and August 2019. Infant weight was assessed and standardized to sex- and age-specific z scores. RWG was defined as weight-for-age z score change > 0.67. Mothers completed questionnaires assessing responsive and pressuring feeding styles, breast- and bottle-feeding patterns, and perceptions of WIC experiences. Logistic regression with estimation via generalized estimating equations and linear mixed models with repeated measures assessed effects of PSE strategies on categorical and continuous outcomes, respectively. Infants in PSE clinics had significantly lower likelihood of exhibiting RWG (P = .014) than infants in control clinics. Mothers in PSE and control clinics reported similar levels of responsive and pressuring feeding style and similar prevalence of breastfeeding and bottle-feeding. Mothers in PSE clinics trended toward feeling better supported with respect to their decision to bottle-feed (P = .098) and had more stable intentions to stay in the WIC program (P = .002) compared with mothers in control clinics. PSE strategies focused on promoting more inclusive assessment of infant feeding, tailored bottle-feeding counseling, and increased education and support for responsive bottle-feeding were associated with lower risk for RWG among WIC infants.