The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) is a highly threatened cetacean endemic to the middle and lower reaches of the Yangtze River that has suffered a dramatic decline in recent decades. We characterize and quantify recent distribution patterns of porpoises in the Yangtze River in order to facilitate strategic management of existing in situ cetacean reserves and maximize effective utilization of limited conservation resources. We calculated porpoise relative abundance (encounter rate) using a 1-km moving average along the Yangtze main stem based on a combined visual and acoustic survey conducted in 2006. We then evaluated conservation priority areas based on encounter rates along the river. High-porpoise density areas (> 0.20 porpoises km−1) cover approximately one-third (33.9%, 599 km) of the survey area and contain approximately two-thirds of the porpoise population, making them priority areas for porpoise conservation. In contrast, low-porpoise density areas (≤ 0.05 porpoises km−1) cover 28.8% (509 km) of the survey area but contain only 4.5% of the porpoise population, and may already be of little value for porpoise conservation. Five high-priority porpoise conservation sites and five sections that now contain few or no surviving porpoises are identified. Proposed spatial modifications to existing reserves and associated conservation recommendations are made for five existing protected areas along the Yangtze main stem, and we emphasize that some additional river sections should urgently be designated as new protected areas given their high porpoise density. Our approach for identifying conservation priorities may provide lessons for reserve design and management in other protected area networks.