Amarillo fine sandy loam is a benchmark soil series in the Southern High Plains (SHP) of Texas, a region known for extensive cotton (Gossypium hirsutum L.) production. Its coarse texture affects the soil's ability to maintain soil organic carbon (SOC) and water storage, which is compounded by the semi-arid climatic conditions and lack of mulch cover to protect the soil from wind erosion. Soil conservation practices such as reduced/no-tillage (NT) and cover cropping are therefore recommended to sequester SOC, increase water storage, and reduce susceptibility to wind erosion. The objective of this study was to evaluate the long-term (1991-2020) effects of NT with cover crops on SHP cotton production systems using the DeNitrification-DeComposition (DNDC) model. Field data (2014-2020) from an experimental site near Lamesa, TX, USA, in the SHP region was used for model calibration and validation. The field experiment included three treatments: conventional tillage without a cover crop (CT, as control), no-till with rye (Secale cereale L.) cover (R-NT), and no-till with mixed cover (M-NT) including rye, hairy vetch (Vicia villosa Roth), radish (Raphanus sativus L.), and winter pea (Pisum sativum L.). The average percent error (PE) between the simulated and measured seed cotton yield was 2.1 % and-4.4 %, and 4.5 % and-8.8 % between the simulated and measured aboveground rye biomass during the calibration and validation, respectively. The 30-year long-term simulations showed that, on average, R-NT and M-NT increased SOC by 40.2 % and 59.2 %, and total nitrogen (TN) by 22.6 % and 25.8 %, respectively, compared to CT. Greater variability in yield and soil water was found under cover crop treatments compared to CT. Overall, the results from this study highlight the potential benefits of cover crops and NT on soil carbon sequestration and TN in semi-arid cotton production systems of the SHP without negatively affecting seed cotton yield.