Biological damage caused by macronutrient deficiency in watermelon plants is still not known, and may lead to nutritional disorders and alterations in absorption and utilization efficiencies, depending on the evaluated nutrient. In this context, the aim of the present study was to evaluate the growth and nutritional efficiency of watermelon plants grown under macronutrient deficiencies. The experiments were carried out in pots containing an aerated nutrient solution. Treatments consisted of the nutrient solution containing (control) or lacking nitrogen (−N), phosphorus (−P), potassium (−K), calcium (−Ca), magnesium (−Mg), and sulfur (−S), in a completely randomized design with three replications. At the end of the experiment with the onset of symptoms of deficiency, plant growth, green color index, nutrient accumulation, nutrient uptake, nutrient utilization efficiency, root density, and foliar deficiency symptoms were evaluated. P, K, Ca, Mg, and S deficiencies increased plant utilization efficiency and can potentiate watermelon development in environments deficient in these nutrients. The opposite was observed concerning nitrogen deficiency, because this condition induced greater biological damage, with low utilization efficiency, indicating the sensitivity of this species in low N conditions.