Background: Soil-transmitted helminths (STH) and schistosomiasis continue to cause serious health problems among affected communities. To ensure that infection transmission levels are reduced, repeated mass drug administration at regular intervals has been recommended by World Health Organization. Preschool age children (PSAC) have been neglected both in terms of research activities and in control programmes in the past for reasons that they carry insignificant infection levels. The current study determined risk factors that contribute to differences in infection prevalence among enrolled and non-enrolled PSAC in Busia County, western Kenya. Methods: This was a comparative cross-sectional study that compared STH and Schistosoma mansoni infections among enrolled and non-enrolled PSAC in Busia County. Simple random sampling was used to select study participants. A total of 327 enrolled and 326 non-enrolled PSAC (n = 653) were recruited from five participating schools, and the neighboring villages. Statistical analysis was performed using STATA version 14 (STATA Corporation, College Station, TX, USA). Differences in proportions were assessed using the z-test statistic for testing sample proportions. Univariable and multivariable logistic regression were used to test the associations between the variables. Results: The prevalence of STH and Schistosoma mansoni infection was 17.0% (95%CI: 13.1-22.1), and 11.8% (95%CI:11.0-12.9) respectively. Specific STH species prevalence were 12.9% (95%CI:7.0-23.5) for Trichuris trichiura, 8.3% (95%CI:8.2-8.3) for Ascaris lumbricoides, and 1.2% (95%CI:1.2-1.2) for hookworms. Prevalence of T. trichiura was higher among enrolled PSAC 16.9% (95%CI: 6.8-41.9); p = 0.003, compared to the non-enrolled 8.9% (95%CI:4.3-18.2). From univariable analysis, lack of improved water source for drinking OR 2.01, (95%CI:1.29-3.13); p = 0.002, and not wearing shoes OR 3.42, (95%CI:1.14-10.29); p = 0.028, were some of the significant factors associated with STH infection. While for multivariable analysis, bathing/ swimming in a river daily, aOR 3.99 (95%CI:1.98-8.06); p = 0.001 was a key significant factor for S. mansoni infections.