The construction industry is a significant source of waste generation in any economy, producing various greenhouse gases, releasing harmful substances into the natural environment, and requiring large areas of land for processing, treatment, and landfilling. The emerging field of off-site prefabrication and assembly is perceived as a viable method to reduce waste and improve sustainability. However, there is a lack of quantifiable research into the difference between off-site prefabrication and on-site, conventional construction for numerous sustainability criteria. This paper focuses on modular construction as an off-site production system, where a framework to compare waste generation of modular and conventional, in-situ construction methods is proposed. This paper aims to quantify these differences. The framework relies on a comprehensive literature review to estimate the waste rates of building materials, which are then applied to realistic case studies in order to determine the differences in waste generation. Overall, modular construction reduces the overall weight of waste by up to 83.2%, for the cases considered. This corresponds to a 47.9% decrease in the cost of waste for large structures. Care must be taken to keep modular wastage as low as possible for a reduced cost of waste to be also present in smaller structures. This reduces the research gap of quantifying the waste differences between conventional and modular construction, and provides thoroughly researched waste rates for future research, while also improving the knowledge of industry stakeholders, informing them of the benefits of modular construction. This allows stakeholders to make more informed decisions when selecting an appropriate construction method.