Coffee production around the world is under threat due to climate variability and change, and drought stress will increase in many coffee regions; nutrient management practices can enhance the adaptation capacity of coffee production. Considering that coffee is a crop sensitive to boron (B) deficiency, this research investigated how B nutrition improves resistance to drought stress in coffee under controlled conditions as well as how the interaction with calcium (Ca2+) influences productivity, seed composition, and soil fertility during a production cycle of 5 years. Under controlled conditions for seven months, coffee plants were submitted to water stress with and without B nutrition. In the field, the coffee plantation was exposed to two B rates (0.6 and 1.1 kg.ha−1-year−1) with a fixed calcium (Ca2+) rate and a control without Ca2+ and B. After 9 months of growth and seven months of water deficit, under controlled conditions, the application of B significantly (p < 0.05) reduced the negative effect of water stress on coffee growth. Under field conditions, after a production cycle of 5 years, the application of 0.6 kg B and 77 kg CaO. ha−1.year−1 yielded 14% more than the control without B and Ca2+. An increase in the B rate to 1.1 kg.ha−1.year−1 with the same Ca2+ rate increased the productivity significantly (p < 0.05) by 37% compared to the control. The B application also improved significantly (p < 0.05) the B content in the soil at 0–30 cm. The B treatments influenced the biochemical composition of the green coffee beans, with a significant (p < 0.05) inverse correlation between the B content of the green coffee beans and caffeine and unsaturated fatty acids (UFAs), mainly, oleic, linoleic, and linolenic acids, which are considered negative descriptors of the coffee quality.