The availability of water and nutrients are determining factors for the growth and productivity of the cucumber crop. The implementation of the grafting techniques increases the efficiency in the absorption of resources such as water and nutrients, improving the quality, mineral content, and enzymatic activity of the fruit. The objective of this research work was to evaluate the effect of the anchor point (soil and substrate), graft (with and without graft), and irrigation volume (100 and 75%) on fruit quality, macro and microelement content, and enzymatic antioxidant activity. A total of eight treatments was established in a completely randomized experiment with a factorial design with a 2 × 2 × 2 arrangement. The results showed an increase in the fruit weight by 10% in grafted plants under 100% irrigation in the substrate, no significant differences between treatments were found in firmness or total soluble solids (TSS). Additionally, while there was a higher accumulation of potassium because of the graft, there was no difference for calcium. It was observed that the enzymatic activity was inhibited using the graft. The graft represents a viable option for the efficient use of water, both in the soil and substrate, being the substrate with the best environment for development, mitigating stress by decreasing enzymatic activity.