The CO2 storage resources and containment effectiveness of deep Cambrian and Ordovician geologic formations were evaluated in eastern Ohio, USA, to evaluate the potential of geologic carbon storage to act as a greenhouse gas reduction strategy in the northwest sub-region of the Appalachian basin. Data compilation, geologic characterization, and storage reservoir and caprock feasibility assessments were conducted following systematic workflows that are consistent with other widely used and internationally recommended approaches for site screening, site selection, and resource classification. Results of this prospective storage resource assessment suggest there are suitable options for deep saline CO2 storage and containment in select areas of central and east-central Ohio. This study provides the foundation of technical expertise and knowledge required to advance carbon capture and storage in the Appalachian basin region. A continued effort is needed to conduct site-specific characterization and ranking of selected areas to determine qualified sites for CO2 injection in the eastern Ohio study area.