Since CO can be reutilized by using renewable electricity in form of product diversity, electrochemical CO reduction (ECR) is expected to be a burgeoning strategy to tackle environmental problems and the energy crisis. Nevertheless, owing to the limited selectivity and reaction efficiency for a single component product, ECR is still far from a large-scale application. Therefore, designing high performance electrocatalysts is the key objective in CO conversion and utilization. Unlike most other types of electrocatalysts, metal-organic frameworks (MOFs) have clear, designable, and tunable catalytic active sites and chemical microenvironments, which are highly conducive to establish a clear structure-performance relationship and guide the further design of high-performance electrocatalysts. This Outlook concisely and critically discusses the rational design strategies of MOF catalysts for ECR in terms of reaction selectivity, current density, and catalyst stability, and outlines the prospects for the development of MOF electrocatalysts and industrial applications. In the future, more efforts should be devoted to designing MOF structures with high stability and electronic conductivity besides high activity and selectivity, as well as to develop efficient electrolytic devices suitable for MOF catalysts.