This study is aimed at comparatively analyzing solid waste management practices and challenges in urban and rural senior high schools in the Ashanti region of Ghana. Multiple sampling techniques (simple random, stratified sampling, convenience sampling, stratified proportionate sampling, etc.) were used to sort 370 samples. Independent Sample -test was used to compare solid waste management practices in rural and urban senior high schools. Mean and standard deviation were further used to examine the challenges the schools faced in managing waste. The study found that both rural and urban senior high schools had waste management practice systems in place but they were dissimilar. However, in both urban and rural senior high schools, the issue of inadequate resources for effective waste management was ubiquitous challenge confronting both set of schools in managing waste. Further, while poor student attitude towards waste management was a major constraint for rural schools, the urban schools had a challenge in terms of poor waste collection routine. Formation of environmental education clubs by school authorities among student can be a sine qua non for effective waste management practices among students, particularly for the rural folks. Again, waste management policies by the District Assemblies should not be exclusive to only the communities, as senior high schools have been experiencing population explosion with the introduction of the free senior high school policy.