In this work, three novel MgO-SiO2 composite catalysts with inverted structure have been synthesized via a facile and scalable strategy by means of the incipient wetness impregnation of the silica sol onto MgO precursors with different morphologies, and evaluated for the one-step conversion of ethanol to 1,3-butadiene. The prepared flower-like MgO-SiO2 composite catalysts exhibited highly enhanced catalytic activity than those catalysts synthesized from MgO precursors with nanodisks and nanosheets morphologies. Characterization results based on XRD, FT-IR, UV vis, BET, CO2-TPD, NH,-TPD, ethanol-TPD, and Si-29 MAS NMR revealed that unique layered flower-like architectures may facilitate the formation of interfacial Mg-O-Si chemical bond in binary MgO-SiO2 composite catalysts which are mainly responsible for the superior activity. This study presents a new strategy to design and develop the catalyst for efficient conversion of bio-ethanol to 1,3-butadiene by morphological control of MgO-SiO2 bifunctional catalysts.