We report the design and synthesis of nanosized ZnxZryOz mixed oxides for direct and high-yield conversion of bio-ethanol to isobutene (similar to 83%). ZnO is addded to ZrO2 to selectively passivate zirconia's strong Lewis acidic sites and weaken Bronsted acidic sites, while simultaneously introducing basicity. As a result, the undesired reactions of bio-ethanol dehydration and acetone polymerization/coking are suppressed. Instead, a surface basic site-catalyzed ethanol dehydrogenation to acetaldehyde, acetaldehyde to acetone conversion via a complex pathway including aldol-condensation/dehydrogenation, and a Bronsted acidic site-catalyzed acetone-to-isobutene reaction pathway dominates on the nanosized ZnxZryOz mixed oxide catalyst, leading to a highly selective process for direct conversion of bio-ethanol to isobutene.