Ecological waterway construction and waterway health protection have become a trend and requirement of waterway development worldwide. How to assess the health status of a waterway is a fundamental concern for waterway sustainable development. This study established a comprehensive framework for health assessment of the waterway from Chongqing to Yibin in the upper reach of the Yangtze River, focusing on the coordinated development of river functions or services including navigation, flood discharge, sediment transport, water supply, self-purification, ecology, and recreation. This framework consists of a hierarchical indicator system, a weight determination method with analytic hierarchy process (AHP), an assessment model considering cask short board effect, and a sensitive analysis method. The waterway health in this river section in the periods 2016–2017 and 2018–2020 were assessed. The results showed that the river functions of navigation, flood discharge, water supply, ecology, and recreation had improved, while sediment transport had deteriorated from “Fair” to “Poor”, and self-purification remained at “Excellent” condition. The overall health of the waterway from Chongqing to Yibin has improved but remained in a “Fair” state during 2016–2020, at roughly the same healthy state as the other three waterways in the middle, middle-lower, and lower reaches. The results are conducive to understanding the health status of the whole Yangtze River waterway. They can serve as an important reference for ecological protection and development of high quality in the Yangtze River basin.