A greenhouse study comparing the physiological responses and uptake of coffee (Coffea arabica L.) plants to foliar applications of zinc sulfate (ZnSO₄) and zinc nano-fertilizer (ZnO NPs) was conducted with the aim to understand their effects on plant physiology. One-year old coffee plants were grown in greenhouse conditions and treated with two foliar applications of 10 mg/L of Zn as either zinc sulfate monohydrate (ZnSO₄ ‧ H₂O) or zinc oxide nanoparticle (ZnO NPs 20% w/t) and compared to untreated control plants over the course of 45 days. ZnO NPs positively affected the fresh weight and dry weight (FW and DW) of roots and leaves, increasing the FW by 37% (root) and 95% (leaves) when compared to control. The DW increase was 28%, 85%, and 20% in roots, stems, and leaves, respectively. The net photosynthetic rate increased 55% in response to ZnO NPs treatment at the end of experiment when compared to control. ZnO NPs-treated leaves contained significantly higher amounts of Zn (1267.1 ± 367.2 mg/kg DW) when compared to ZnSO₄-treated plants (344.1 ± 106.2 mg/kg DW), while control plants had the lowest Zn content in the leaf tissue (53.6 ± 18.9 mg/kg DW). X-ray micro-analyses maps demonstrated the increased penetrance of ZnO NPs in coffee leaf tissue. Overall, ZnO NPs had a more positive impact on coffee growth and physiology than conventional Zn salts, which was most likely due to their increased ability to be absorbed by the leaf. These results indicate that the application of ZnO NPs could be considered for coffee systems to improve fruit set and quality, especially in areas where Zn deficiency is high.