Cotton suffers from alternations of flood and drought in China. A lysimeter trial was conducted to investigate the responses of various cotton yield indices under water-stress treatments including, flood (five-day, eight-day), drought (10-day, 15-day), and five-day flood followed by 10-day drought, during the flowering and boll-forming stage. The results showed that the seed cotton yield was significantly (p < 0.05) reduced under all water-stress treatments, while the harvest index was not affected under any treatment. Significant decreases in dry matter yield, boll number, and boll hull mass were detected under flood treatments but not under drought treatments. The percentage cotton yield losses per day induced by flood and drought were 6.22% and 2.48%, respectively. Under water stress, the associations between seed cotton yield and relevant yield indices were weakened, but yield losses were still strongly related to the decreases in dry matter yield and boll number. Flood followed by drought caused significant reductions in all yield indices except harvest index; however, the reduction was much lower than the additive reductions induced by flood and drought. These results provide bases for scheduling irrigation and drainage under climate change.