Landuse change from native prairie to managed agriculture can have substantial impacts on soil nutrient properties. Nutrient release from soil organic matter decomposition is the soil’s inherent source of long-term fertility; thus it is imperative to understand the effects of continued landuse over time to avoid mistaking actual soil property changes with simple inter-annual variability from one year to the next. The objective of this study was to evaluate the effects of landuse (i.e. managed agriculture and native prairie) in two contrasting physiographic regions (i.e. the Ozark Highlands region of northwest Arkansas and the Grand Prairie region of east-central Arkansas) on the change in extractable soil nutrients over a 15-yr period from 2001 to 2016. Extractable soil Ca, Mg, and Zn increased at least two times more over time (P Averaged across landuse, extractable soil S increased nine times more over time (P P Averaged across region, extractable soil Mn increased 2.5 times more over time (P < 0.05) under native prairie than under agricultural landuse. Results from this long-term field study clearly demonstrate how landuse and regional soil characteristics can affect near-surface soil nutrient contents, which should be taken into consideration when implementing conservation and/or ecosystem restoration activities.