Amblyomma americanum (L.), the lone star tick, is a vector of pathogens in humans and other animals throughout the United States. Our objective was to characterize how environmental factors influence patterns of A. americanum activity throughout its life cycle by creating statistical models that describe the number of active off-host larvae, nymphs, and adults in northeast Missouri from 2007 to 2013. Ticks were collected every other week from a permanent sampling grid in a second-growth forest and in an old field habitat. Each of the three life stage models considered six meteorological variables and one biotic variable. Regression modeling was used to make candidate models which were evaluated with eight selection criteria. Best-selected models were useful in describing seasonality and magnitude of A. americanum activity for larvae, nymphs, and adults. While distinct subsets of environmental variables were optimal in each life stage, all three models incorporated cumulative degree days, habitat, and number of ticks in the previous life stage. These models further elucidate how environmental and demographic factors influence patterns of host-seeking activity throughout the A. americanum life cycle, providing insight into how changing climate may impact risk of tick-borne pathogen transmission.