Abstract: In response to climate change, runoff in the headwaters of the Yangtze River has exhibited significant variations over recent decades, with pronounced seasonal differences. This study utilized daily discharge data from 1980 to 2022 at the Zhimenda hydrological observation station, located in the headwater region of the Yangtze River, and applied Principal Component Analysis (PCA) to examine seasonal runoff variability and its impact factors. The results indicate that, ① Five distinct seasonal characteristic periods of runoff variation were identified: winter-spring (December to April of the following year), autumn (September to November), late spring to early summer (May to July), midsummer (July to August), and early May; ② The winter-spring period (December–April) demonstrated the most prolonged consistent trend, characterized by relatively low total runoff but a marked phased increase, with an annual growth rate of approximately 320 m³/s, representing a 38.9% increase over the 43-year period. Autumn runoff exhibited a significant and sustained linear increasing trend, with an annual growth rate of 2.0%, making it the period with the most substantial runoff increase. During the summer half-year (May–July and July–August), runoff trends were statistically insignificant, yet two distinct interannual variation patterns were observed. Unlike other periods, early May showed a slight declining trend in runoff; ③ The phased increase in runoff during the winter half-year was directly associated with rising air temperatures, with a partial correlation coefficient of 0.519 (p < 0.001). Runoff in July–August was predominantly controlled by precipitation, showing a partial correlation coefficient of 0.694 (p < 0.001). Runoff variations in other periods were jointly influenced by both precipitation and temperature; ④ An abrupt temperature shift around 2011 further affected runoff regimes, leading to a weakened dominance of single climatic factors and an increasingly compounded influence of multiple factors thereafter. This study reveals seasonal runoff variations in the context of climate warming and moistening on the Tibetan Plateau, providing valuable insights into the complexity of runoff changes and supporting regional water resource management.