We report the design and synthesis of nanosized Zn(x)Zr(y)O(z) mixed oxides for direct and high-yield conversion of bio-ethanol to isobutene (~83%). ZnO is addded to ZrO(2) to selectively passivate zirconia's strong Lewis acidic sites and weaken Brönsted 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 Brönsted acidic site-catalyzed acetone-to-isobutene reaction pathway dominates on the nanosized Zn(x)Zr(y)O(z) mixed oxide catalyst, leading to a highly selective process for direct conversion of bio-ethanol to isobutene.