Colorectal cancer is a leading cause of cancer death in Uruguay, yet less than half of the eligible population is up to date with screenings. Research is hampered because no measures exist to assess psychosocial factors that influence screening decisions in this population. To address this gap, we report on the development and psychometric validation of the Colorectal Cancer Literacy Scale—Uruguay Version, a scale based on the health literacy model. We developed an item pool based on the extant literature, obtained feedback from experts, and conducted focus groups with community participants and health care providers. After revision, we conducted a psychometric validation with a national community sample of 405 participants. Through an exploratory factor analysis, we identified four factors that were collapsed into two for theoretical and pragmatic reasons, representing (a) disposition toward cancer prevention and (b) attitudes, beliefs, and emotions about cancer. A third factor, knowledge about colorectal cancer, was examined separately given its distinct focus. Subsequently, we conducted a confirmatory factor analysis with the remaining sample participants using Rasch measurement theory for validation purposes and to further assess the scales’ psychometric properties. The resulting 44-item scale presented a good model fit with adequate EAP reliabilities and good initial discriminant validity. Further criterion-related validity analyses should be performed when additional measures are available. The Colorectal Cancer Literacy Scale—Uruguay Version is a theoretically based measure that can bring to light barriers and facilitative factors in an underscreened population at risk. Implications for theory, research, and practice are discussed.