This study examines the role of entrepreneurial orientation (EO) and collaborative engagement on the performance of rural economic development organizations. The authors theorize that an organization’s EO and collaborative engagement, determined by levels of active engagement within a regional collaboration network, impact its ability to accomplish its goals, satisfy its stakeholders, and influence regional economic development. The authors’ analysis of data from 98 collaborating economic development organizations operating in the economically distressed region of eastern Kentucky shows that EO and collaborative engagement are positively associated with performance. This study provides actionable insights for leaders of economic development organizations seeking to improve their operations.