Agriculture—specifically an intensification of the production of readily stored food and its distribution—has supported an increase in the global human population throughout the Holocene. Today, with greatly accelerated of growth during recent centuries, we have reached about 8 billion people. Human skeletal and archaeobotanical remains clarify what occurred over several millennia of profound societal and population change in small-scale societies once distributed across the North American midcontinent. Stepwise, not gradual, changes in the move toward an agriculturally based life, as indicated by plant remains, left a demographic signal reflecting age-independent (
α
2
) mortality as estimated from skeletons. Designated the age-independent component of the Siler model, it is tracked through the juvenility index (JI), which is increasingly being used in studies of archaeological skeletons. Usually interpreted as a fertility indicator, the JI is more responsive to age-independent mortality in societies that dominated most of human existence. In the midcontinent, the JI increased as people transitioned to a more intensive form of food production that prominently featured maize. Several centuries later, the JI declined, along with a reversion to a somewhat more diverse diet and a reduction in overall population size. Changes in age-independent mortality coincided with previously recognized increases in intergroup conflict, group movement, and pathogen exposure. Similar rises and falls in JI values have been reported for other parts of the world during the emergence of agricultural systems.