The diffusion of no-tillage (NT) is to be encouraged because of the benefits it can provide in terms of improving soil fertility and counteracting global warming and climate change as part of climate-smart agriculture practices. However, the introduction of this management can be difficult, especially in the first years of application, and can lead to unpredictable yield results depending on the soil type. Therefore, the aim of this experiment was to evaluate the early effect of NT use, compared to the conventional mouldboard ploughing (CT), on two different soils, a clay-loam (GAL) and a sandy-clay-loam soil (SMA), by monitoring a set of 43 different soil and plant variables that were expected to vary with tillage and/or soil type. At both experimental sites, NT showed lower wheat total biomass (−29%) and grain yields (−17%) than CT with a more pronounced decrease in GAL than in SMA. Yield differences were accompanied by modifications in nutrient, microbial community and soil enzyme activity dynamics which highlighted higher stress in GAL, than in SMA soil, attributable to lower crop residues decomposition and substrate availability. Therefore, our findings suggest that the negative consequences due to the transition to NT depend on specific soil characteristics, like texture and organic matter concentration, with different repercussions on soil quality as well as on wheat growth and productivity.