Abstract: Hot–dry periods with low rain and high temperatures along MLRYR (the middle and lower reaches of the Yangtze River) have significant effects on agriculture, water conservation, and human health. However, there is still a lack of sufficient understanding of the historical divisions and long-term change patterns of the hot–dry period in the region. Based on the daily temperature and precipitation data of the Meiyu and summer seasons from five stations (Shanghai, Nanjing, Wuhu, Jiujiang, and Hankou) along the MLRYR since 1885, the quantitative standards of low rain and high temperature for the hot–dry period after the Meiyu season were determined, and the MLRYR hot–dry periods from 1885 to 2020 were defined. By combining the uniform temperature standard and the length of the summer hot–dry period, the intensity index of the summer hot–dry period for 136 years was determined. For the 136 years, the annual hot–dry period had an average length of 21.6 d (including 16 non-hot–dry-period years and 10 autumn hot–dry years), exhibiting cycles of 3–6 years, 36 years, and 84 years. Since 1951, 1959–1978 has been the main peak period with long annual hot–dry periods, while 1980–1987 has been the valley period, and then the number of hot–dry days slowly increased. After the 1980s, even though long hot–dry periods more than 30 days tended to decrease, high-intensity hot–dry periods of 15–30 days frequently occurred. Since 1995, the number of the autumn hot–dry days has increased significantly, and summer has shown a trend of delay. The years 1934, 1967, 1978, and 2013 showed the longest and strongest summer hot–dry periods in 136 years, and the earliest/latest hot–dry period was observed in the middle of June/middle and late September. In the past 40 years, the number of high-temperature days (≥35.0°C) in the summer hot–dry periods has increased significantly, and the incidence of high temperature in the summer hot–dry periods has increased from approximately 30% in the 1980s to more than 50% in recent years, posing a threat to human health. The characteristics of subtropical circulation in the long (strong) summer hot–dry periods are that the western Pacific subtropical high stably controls the MLRYR, while in the short (weak) summer hot–dry periods, the western Pacific subtropical high is mostly located in the east or south, and the autumn hot–dry periods are associated with the stable westward extension of the subtropical high. The increase of high-temperature days in the summer hot–dry periods is restricted by two human activities: (1) Global sea and land warming; (2) the evolution of the local ecological environment and change in urban heat island effects. On the interdecadal timescale, the continent–ocean temperature difference in the Indo-Pacific monsoon region has a significant modulation effect on the interdecadal variation in the length of the summer hot–dry periods along the MLRYR.