Context The no-till (NT) system is used to control soil erosion and nutrient losses, but extensive evaluation of NT on soil health and long-term crop yields compared to conventional till (CT) is needed to evaluate the overall benefit of NT. Aims The objective of this study was to compare NT and CT on soil health and long-term crop yields in two dryland farming sites in the northern Great Plains, USA. Methods Soil samples collected from two long-term (14- and 36-years-old) experiments of dryland farming under NT and CT continuous spring wheat (Triticum aestivum L.) and barley (Hordeum vulgaris L.)/spring wheat-fallow rotation were analysed for 66 soil physical, chemical, biological and biochemical properties and crop yields determined. Key results NT increased wet soil stability index, average slake aggregate and total shrinkage by 12–61%, but reduced saturated hydraulic conductivity by 24–31% compared to CT. Soil Al, Ba, Cu and S concentrations were 10–16% greater, but electrical conductivity, Co, Na and Zn concentrations, and Na-absorption ratio were 9–33% lower with NT than CT. Similarly, NH4-N concentration, CO2 evolution, phospholipid-derived fatty acid (PLFA), phosphomonoesterase and arysulfatase were 13–38% greater, but water extractable N, NO3-N concentration and potential N mineralisation were 16–31% lower with NT than CT. Mean crop yield across years were similar between NT than CT. Conclusions NT can enhance overall soil health and sustain dryland crop yields compared to CT in the northern Great Plains, USA. Implications Long-term sustainability of dryland cropping system can be maintained by using the NT system.