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<h4>Background</h4> Trachoma is the leading infectious cause of blindness. To reduce transmission, water, sanitation, and hygiene (WaSH) improvements are promoted through a comprehensive public health strategy. Evidence supporting the role of WaSH in trachoma elimination is mixed and it remains unknown what WaSH coverages are needed to effectively reduce transmission. <h4>Methods/Findings</h4> We used g-computation to estimate the impact on the prevalence of trachomatous inflammation—follicular among children aged 1–9 years (TF1-9) when hypothetical WaSH interventions raised the minimum coverages from 5% to 100% for “nearby” face-washing water (<30 minutes roundtrip collection time) and adult latrine use in an evaluation unit (EU). For each scenario, we estimated the generalized prevalence difference as the TF1-9 prevalence under the intervention scenarios minus the observed prevalence. Data from 574 cross-sectional surveys conducted in 16 African and Eastern Mediterranean countries were included. Surveys were conducted from 2015–2019 with support from the Global Trachoma Mapping Project and Tropical Data. When modeling interventions among EUs that had not yet met the TF1-9 elimination target, increasing nearby face-washing water and latrine use coverages above 30% was generally associated with consistent decreases in TF1-9. For nearby face-washing water, we estimated a ≥25% decrease in TF1-9 at 65% coverage, with a plateau upon reaching 85% coverage. For latrine use, the estimated decrease in TF1-9 accelerated from 80% coverage upward, with a ≥25% decrease in TF1-9 by 85% coverage. Among EUs that had previously met the elimination target, results were inconclusive. <h4>Conclusions</h4> Our results support Sustainable Development Goal 6 and provide insight into potential WaSH-related coverage targets for trachoma elimination. Targets can be tested in future trials to improve evidence-based WaSH guidance for trachoma. Author summary Previous work has been unable to determine what water, sanitation, and hygiene (WaSH)-related coverages are needed to optimally limit trachoma transmission. This study uses a large, multi-national dataset to explore the impact of hypothetical WaSH interventions designed to increase coverages of face-washing water and latrine use in districts that have met and those that have not met trachoma elimination targets. We used statistical models to explore how these interventions impacted the prevalence of trachoma among children as compared to the observed data. Our findings provide evidence-based insight into potential WaSH coverage targets that could be hypothesized to achieve meaningful reductions in trachoma prevalence. We found that in areas working to reach trachoma elimination targets, increasing face-washing water and latrine use coverages to a minimum of ≥30% were consistently associated with (modelled) reductions in active trachoma prevalence. However, in areas that had already met trachoma elimination targets, we did not see the same pattern. This finding supports our theory that the WaSH-trachoma relationship differs in these areas and suggests a need for additional research to explore these relationships. Our estimates can be used to inform programmatic WaSH targets and future field trials.