Background: Community-based behavior change interventions are a common approach to Water, Sanitation, and Hygiene (WASH). Yet, published evaluations of how these interventions work in district-wide approaches are rare. Objective: This study reports the baseline characteristics and study design for a trial assessing the effectiveness of a district-level Community-led Total Sanitation (CLTS) intervention compared to the additional integration of local care groups (CG) on sanitation coverage and use and hygiene behaviors in Chiradzulu District, Malawi. Methods: This study is a controlled before-and-after trial with 2 treatment arms and a control group. Clusters are rural villages in 3 traditional authorities (TAs). One arm will receive CLTS and the CG model (CLTS+CG group), one arm CLTS only (CLTS group), and one group will serve as the control. The trial is part of the wider WASH for Everyone (W4E) project, led by World Vision Malawi that aims to expand access to WASH services across the entire district by 2025. Study participants were selected from the 3 TAs. Systematic sampling procedures were used to select 20 households per cluster with a total of 1400 households at both baseline and end line. The primary outcome is sanitation coverage. Secondary outcome measures include sanitation use, safe disposal of child feces, observed handwashing facility, and Sanitation-related Quality of Life Index (SanQoL-5). Results: The baseline observations indicate a balanced distribution of potential demographic confounders in the trial arms with a slight variation on some WASH proxy measures. We noted the low coverage of handwashing facilities with soap and water in all 3 arms: 8% in the CLTS group, 4% in the CLTS+CG group, and 4% in the control group. There was a marginal variation in handwashing practices among the study arms with 3% of individuals handwashing with soap and water in the CLTS group, 5% in the CLTS+CG group, and 2% in the control group. Sanitation coverage also varied among the study arms at baseline as 83% of households had access to unimproved sanitation in the CLTS group, 70% in the CLTS+CG group, and 81% in the control group. Conclusions: Results from this trial will provide evidence on whether the CLTS+CG approach is effective at improving sanitation and hygiene practices in the W4E program area compared to CLTS alone and no intervention, as well as inform implementing partners on future interventions in Chiradzulu District, Malawi. The results are expected to be published in 2025. Trial Registration: ClinicalTrials.gov NCT05808218; https://clinicaltrials.gov/study/NCT05808218. International Registered Report Identifier (IRRID): RR1-10.2196/68280