Sugarcane vinasse management is one of the biggest challenges of distilleries around the world. Vinasse can be used for crop fertigation, but it requires a prior conditioning treatment. This study investigates the short-term effect of the fertigation with raw vinasse (V0) and vinasse biologically treated with the filamentous fungus Aspergillus sp. V2 (Vt) on the growth of Triticum aestivum L. (wheat), soil nutrient replenishment and soil enzyme activities. Effects of commercial chemical fertilizer (NPK) and water tap (Wt) on the parameters studied were also analyzed. The fertigation with Vt had positive effects on wheat, increasing all the plant growth parameters compared with V0, NPK and Wt. Fertigation with Vt also induced positive changes in soil with respect to the other solutions tested, favoring the replenishment of organic matter and nutrients such as potassium (K), phosphorous (P), and magnesium (Mg). Moreover, soil enzymes (particularly dehydrogenase enzyme) responded differentially to changes in the fertigation conditions tested, providing reliable information on system quality. These results demonstrate that a fungal-based pretreatment improves the vinasse properties for agricultural uses, contributing to the advance towards a bio-based circular economy.