The American Kestrel (Falco sparverius), a small, cavity-nesting falcon that breeds across most of North America, is experiencing an apparent population decline across much of the United States that has yet to be sufficiently explained. With landscape change as a potential factor, the association of landscape composition with kestrel reproduction may assist not only in managing declines but also in improving the effectiveness and efficiency of nest box programs, which can bolster local populations and support monitoring and research efforts. We monitored 163 unique American Kestrel nest boxes over a 12-yr study period (2008–2019) in western Virginia to investigate the factors influencing kestrel reproductive success and we documented relatively high rates of both box occupancy (80%) and nest success (78.9%). In a study area dominated by both high- and low-intensity agriculture, we focused on identifying patterns in land cover composition that may limit reproductive success and associated each box with land cover composition metrics at four spatial scales. Generalized linear mixed models indicated nest boxes with a lower proportion of developed land within 500 m, and a higher proportion of crops and pasture/hay within 3 km were more likely to be occupied by kestrels. Although probability of kestrel nest success increased with reduced proportions of developed land within 100 m, the primary factors influencing success were clutch initiation date and the presence of European starlings (Sturnus vulgaris), with earlier nesting and the absence of starling activity resulting in higher nest success. Overall, cover-type associations with nest success and box occupancy were not strong and establishment of nest boxes in targeted kestrel habitat, while likely maximizing reproductive output, limits research opportunities to identify critical land cover thresholds for the species.