Over a decade after the forest-savanna transition zone of Nigeria was deemed suitable for production of sorghum (Sorghum bicolor), no research has been undertaken on the crop's tillage requirements in the southeastern part of the zone. This study evaluated the effects of tillage-mulch practices on soil moisture, water use (WU), grain yield and water use efficiency (WUE) of the crop in a Typic Paleustult (sandy loam) at Nsukka during 2006 and 2007 growing seasons. In a split-plot design, no-till (NT) and conventional tillage (CT) treatments were left bare (B) or covered with mulch (M) at 5 Mg ha−1. The ensuing treatments (NTB, NTM, CTB, and CTM) represented four tillage methods, which were replicated four times in a randomized complete block. In the monitored root zone, NTB and CTM significantly (p ≤ 0.05) enhanced the soil moisture status over NTM and CTB, but the main effects of the tillage and the mulch factors were not significant. The crop WU was uninfluenced by the treatments throughout the study. Although the grain yield showed higher values with NT than with CT, the differences were significant (p ≤ 0.05) only in 2007 that was marked with erratic rainfall and relatively low mean yield. Mulch significantly (p ≤ 0.05) enhanced the grain yield in 2006, with greater effect in CT than NT. On average, the mulch plots out-yielded their bare counterparts by about 26%. The tillage × mulch interaction was significant (p ≤ 0.01), and showed higher grain yields in NTB, NTM and CTM than in CTB. In the year-weighted average, yield increments in NTB, NTM and CTM over CTB were 53, 53 and 67% respectively, a pointer to the relevance of mulch with the CT but not the NT. Relative WU showed that the crop's water demand was met under all treatments. Hence, the yield reduction in the CTB was not due to water shortage. The WUE varied among the treatments in the same pattern as grain yield. In summary, NTB and CTM proved superior to NTM only in soil moisture status but to CTB in all measured parameters. From a socio-economic viewpoint, however, NTB would be preferable to CTM for growing sorghum in this area.