Unhealthy diets and a lack of exercise in children are leading to metabolic disorders in adults. This dissertation characterized effects of early-life experiences (phenotypic plasticity) on adult activity levels by altering the diet and/or exercise of juvenile mice. Subjects were from a selection experiment in which four replicate lines of High Runner (HR) mice evolved to run 2.5-3-fold more wheel revolutions per day than those from four non-selected Control (C) lines. Expectations were that 1) early-life experiences would have long-lasting effects into adulthood, 2) early-life factors would have interactive effects, and 3) genotype-by-environment interactions would occur). Chapter 1 considered effects of early-life high fat, high sugar diet and/or exercise on adult physical activity. Juvenile mice were exposed to 3 weeks of Western diet (WD) and/or wheel access, beginning at weaning, followed by an 8-week washout period (~6 human years). In adults, early exercise increased wheel running of C but not HR mice, decreased anxiety-like behavior and heart ventricle mass, but increased fasted blood glucose levels, triceps surae, subdermal fat pad, and brain masses. In contrast, early-life WD increased adult wheel running of HR but not C mice. Chapter 2 exposed mice to similar early-life treatments, except WD was replaced with fructose in drinking water to assess its potential to suppress activity levels acutely and into adulthood after a 23-week washout period. One HR and one C line were used. As in Chapter 1, early exercise increased adult running, but also decreased adult fat mass. Early-life fructose increased fat mass acutely but had inconsistent effects on wheel running and cage activity, with no long-lasting effects into adulthood. Chapter 3 was a cross-fostering experiment designed to test the importance of the early postnatal maternal environment in the development of the HR phenotype. Fostering C pups to HR dams did not increase the wheel running of C adults, nor did fostering HR pups to C dams suppress running of HR adults. These studies demonstrate that early-life experiences can have both acute and long-lasting effects on various traits, including physical activity, and that those effects interact with genetic background.