The road network is a major urban lifeline, and its post-earthquake resiliency is crucial to rapid and reliable rescue work. This study aims to optimize risk mitigation investment strategies for improving post-earthquake road network resilience. First, instead of theoretical assumptions on link failure probability, an empirical predictive model of debris obstruction of collapsed buildings was used to calculate link connectivity probability. Second, the Monte Carlo simulation method was employed to calculate post-earthquake road network accessibility based on the results of link connectivity reliability. Third, an optimal risk mitigation investment model was used in order to maximize post-earthquake network accessibility with different government budgets. A case study was analyzed by using the proposed method in an Shanghai historical area. Results may help local governments make better decisions of risk mitigation strategies in regard to earthquakes.