Evaluating the effectiveness of nature reserves is crucial for promoting regional sustainable development. The Yangtze River Economic Belt of China is a hub of biodiversity. So, evaluating the effectiveness of nature reserves in this region is important to enhance its management and ecological civilization. Based on global human footprint datasets, this study analyzed the changes of the human disturbance in nature reserves in the Yangtze River Economic Belt during 2000-2018 from the perspectives of management levels, geographical economic zones, and functional zones. Then the propensity score matching method was used to assess the effectiveness of nature reserves in reducing human disturbance. The major findings are as follows: ① The number of nature reserves with excellent, good, and poor protection effectiveness in the Yangtze River Economic Belt accounted for 35.12%, 50.30%, and 14.58%, respectively. ② The human footprint values of the Yangtze River Economic Belt and its nature reserves were increasing overall, but the latter increase was less than half of the former. It suggests that although establishing nature reserves in this region has not changed the trend of increasing human footprint, it has effectively slowed down its growth. ③ The higher the management level of nature reserves and their functional zones, the better protection effectiveness. ④ The effectiveness of nature reserves in the upper and middle reaches of the Yangtze River Economic Belt was better than that in the lower regions, particularly in the Ba Mountain-Wu Mountain-Wuling Mountain-Xuefeng Mountain area and the western part of Yunnan. These findings can provide a reference for enhancing the management of nature reserves in the Yangtze River Economic Belt and promoting ecological civilization construction for this region, and even in China.