The one-pot conversion of ethanol to butadiene is a promising route for butadiene production; however, simultaneous attainment of high butadiene productivity and high butadiene selectivity is challenging. Here, zeolite-confined bicomponent Zn–Y clusters were constructed and applied as robust catalysts for ethanol-to-butadiene conversion with a state-of-the-art butadiene productivity of 2.33 gBD/gcat/h and butadiene selectivity of ∼63%. Structural confinement effects are responsible for the enhanced butadiene production efficiency via a multiple-step cascade reaction.