The development of new, improved zeolitic materials is of prime importance to progress heterogeneous catalysis and adsorption technologies. The zeolite HZSM-5 and metal oxide γ-Al2O3 are key materials for processing bio-alcohols, but both have some limitations, i.e., HZSM-5 has a high activity but low catalytic stability, and vice versa for γ-Al2O3. To combine their advantages and suppress their disadvantages, this study reports the synthesis, characterization, and catalytic results of a hybrid nano-HZSM-5/γ-Al2O3 catalyst for the dehydration of n-butanol to butenes. The hybrid catalyst is prepared by the in-situ hydrothermal synthesis of nano-HZSM-5 onto γ-Al2O3. This catalyst combines mesoporosity, related to the γ-Al2O3 support, and microporosity due to the nano-HZSM-5 crystals dispersed on the γ-Al2O3. HZSM-5 and γ-Al2O3 being in one hybrid catalyst leads to a different acid strength distribution and outperforms both single materials as it shows increased activity (compared to γ-Al2O3) and a high selectivity to olefins, even at low conversion and a higher stability (compared to HZSM-5). The hybrid catalyst also outperforms a physical mixture of nano-HZSM-5 and γ-Al2O3, indicating a truly synergistic effect in the hybrid catalyst.