Floods and droughts and their effects on Hohokam canal systems and irrigation agriculture play a prominent role in many cultural-historical interpretations of the Hohokam trajectory in the lower Salt River valley (modern-day Phoenix, Arizona metropolitan area). Catastrophic floods and associated geomorphic stream channel changes may have contributed to settlement and population changes and the substantial depopulation of the lower Salt River valley ca. A.D. 1450 or later. In this study, archaeological data on Hohokam domestic architecture is used to infer changes in prehistoric population growth rates from ca. A.D. 775 through 1450 in the most thoroughly documented canal system in the Salt River valley. Changes in growth rates are compared to the retrodictions of annual streamflow discharge volumes derived from tree-ring records. Contrary to expectations, population growth rates increased as the frequency, magnitude, and duration of inferred flooding, drought, and variability increased. These results challenge existing assumptions regarding the relationship among floods and droughts, conditions for irrigation agriculture, and population change in the lower Salt River valley.