CO2 capture and storage (CCS) is a climate-change mitigation technology that can significantly reduce greenhouse gas emissions in the near future. To have a meaningful impact, CCS infrastructure will have to be deployed on a massive scale; in the U.S. this will require capturing CO2 from hundreds of fossil fuel power plants and building a dedicated pipeline network to transport a volume of CO2 greater than domestic oil consumption. In this paper, we analyze the effect of geologic reservoir uncertainty on constructing CCS infrastructure—geologic uncertainty can impact reservoir cost and capacity estimates by as much as an order of magnitude. This uncertainty propagates through the capture–transport–storage system, influencing decisions including where and how much CO2 should be captured. We demonstrate the effect of geologic uncertainty using a proposed oil shale industry that could generate tens of millions of tonnes of CO2 each year. We show that uncertainty can make transport and storage costs deviate by over 100% and that CCS infrastructure, particularly the optimal pipeline network, can considerably diverge spatially. Finally, we draw conclusions on how geologic uncertainty may end up being a driving factor on how major industries decide to manage produced CO2.