The population of Pueblo Grande probably reached its peak in the Classic Period, with as many as 1000 people living in the village. At its largest extent it is estimated that the size of the village was approximately 500 acres or one mile in diameter. Studies of burials excavated from the site indicate that the population was suffering from malnutrition, despite their utilization of all available resources, including the intensive harvesting of fish from the Salt River and local irrigation canals.
Large floods recorded for the Salt River in A.D. 1358 and 1380-1382 probably contributed to the collapse and/or restructuring of Hohokam society at Pueblo Grande and elsewhere during the 1400's. Around A.D. 1450 the Hohokam abandoned Pueblo Grande as well as other villages in the Salt River Valley. For reasons still under investigation, more than 1000 years of occupation at Pueblo Grande came to an end.