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Background: Globally, nearly 250 million children (43% of all children under 5 years of age) are at risk of compromised neurodevelopment due to poverty, stunting, and lack of stimulation. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH) and improved infant and young child feeding (IYCF) on early child development (ECD) among children enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Methods and findings: SHINE was a cluster-randomized community-based 2×2 factorial trial. A total of 5,280 pregnant women were enrolled from 211 clusters (defined as the catchment area of 1–4 village health workers [VHWs] employed by the Zimbabwean Ministry of Health and Child Care). Clusters were randomly allocated to standard of care, IYCF (20 g of small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counseling), WASH (ventilated improved pit latrine, handwashing stations, chlorine, liquid soap, and play yard), and WASH + IYCF. Primary outcomes were child length-for-age Z-score and hemoglobin concentration at 18 months of age. Children who completed the 18-month visit and turned 2 years (102–112 weeks) between March 1, 2016, and April 30, 2017, were eligible for the ECD substudy. We prespecified that primary inferences would be drawn from findings of children born to HIV-negative mothers; these results are presented in this paper. A total of 1,655 HIV-unexposed children (64% of those eligible) were recruited into the ECD substudy from 206 clusters and evaluated for ECD at 2 years of age using the Malawi Developmental Assessment Tool (MDAT) to assess gross motor, fine motor, language, and social skills; the MacArthur–Bates Communicative Development Inventories (CDI) to assess vocabulary and grammar; the A-not-B test to assess object permanence; and a self-control task. Outcomes were analyzed in the intention-to-treat population. For all ECD outcomes, there was not a statistical interaction between the IYCF and WASH interventions, so we estimated the effects of the interventions by comparing the 2 IYCF groups with the 2 non-IYCF groups and the 2 WASH groups with the 2 non-WASH groups. The mean (95% CI) total MDAT score was modestly higher in the IYCF groups compared to the non-IYCF groups in unadjusted analysis: 1.35 (0.24, 2.46; p = 0.017); this difference did not persist in adjusted analysis: 0.79 (−0.22, 1.68; p = 0.057). There was no evidence of impact of the IYCF intervention on the CDI, A-not-B, or self-control tests. Among children in the WASH groups compared to those in the non-WASH groups, mean scores were not different for the MDAT, A-not-B, or self-control tests; mean CDI score was not different in unadjusted analysis (0.99 [95% CI −1.18, 3.17]) but was higher in children in the WASH groups in adjusted analysis (1.81 [0.01, 3.61]). The main limitation of the study was the specific time window for substudy recruitment, meaning not all children from the main trial were enrolled. Conclusions: We found little evidence that the IYCF and WASH interventions implemented in SHINE caused clinically important improvements in child development at 2 years of age. Interventions that directly target neurodevelopment (e.g., early stimulation) or that more comprehensively address the multifactorial nature of neurodevelopment may be required to support healthy development of vulnerable children. Trial registration: ClinicalTrials.gov NCT01824940 In this substudy from a 2x2 factorial cluster-randomized trial, Melissa Gladstone and colleagues assess whether improved WASH and/or feeding provide a benefit to early child development. Author summary: Why was this study done?: Some 43% of children globally fail to reach their full developmental potential due to stunting and poverty. Current evidence shows that improved nutrition has a modest effect on early child development. Improving water, sanitation, and hygiene (WASH) may plausibly benefit neurodevelopment through reduced illness and improved gut health (through improving nutrient absorption and optimizing gut–brain communication). What did the researchers do and find?: The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial tested the individual and combined effects of improved complementary feeding (provision of a small quantity of lipid-based nutrient supplement from 6 to 18 months of age, with complementary feeding counseling) and improved household WASH (provision of a pit latrine, handwashing stations, soap, chlorine, and hygiene counseling) on early child development at 24 months. In all, 1,655 children born to HIV-negative women were assessed for gross motor, fine motor, language, cognitive, and social development using tools that were designed and adapted for rural Zimbabwe. We found little evidence that the complementary feeding or WASH interventions tested improved child neurodevelopment at 2 years of age. What do these findings mean?: Complementary feeding and WASH interventions (as described above) may not have a clinically significant impact on child neurodevelopment. More holistic approaches and interventions that explicitly target early child development may be needed to substantially impact child neurodevelopment. [ABSTRACT FROM AUTHOR]