The Ozark Highlands is a unique botanical transition zone where native prairie and forest once co-existed, but conversion to managed agricultural landuse has severely reduced the extent of native tallgrass prairie. Quantifying soil nutrient changes over time can contribute to improved understanding of the importance of soil fertility in prairie restoration success. The objective of this study was to evaluate the effects of prairie ecosystem [i.e., chronosequence of four prairie restorations and a native prairie (NP)] and soil moisture regime (SMR; aquic and udic) on the change in extractable soil nutrients over a 12-yr period from 2005 to 2017 in the Ozark Highlands region of northwest Arkansas. Soil Ca content decreased over time (P ≤ 0.05) in the 17-year-old-aquic and NP-udic combinations, which did not differ and averaged ?55.7 kg?ha?1?yr?1, but did not change over time in all other ecosystem-SMR combinations. Soil Na content also decreased over time (P ≤ 0.05) in the 17-year-old-aquic combination (?0.7 kg?ha?1?yr?1), but did not change over time in any of the other ecosystem-SMR combinations. Averaged across SMR, soil P content decreased over time (P ≤ 0.05) in the 17-year-old restoration (?1.6 kg?ha?1?yr?1), while did not change over time in the other three restorations and NP. Soil K, Mg, and Zn content changes over time did not differ (P > 0.05) among ecosystem or between SMRs. Soil nutrient changes are manifestations of soil organic matter dynamics over time and contribute to the inherent soil fertility status of an ecosystem, which needs to be balanced for proper ecosystem functioning and restoration success.