Dehydrogenation coupling of ethanol to n-butanol has received much attention due to the wide application of n-butanol. Highly selective butanol production from ethanol remains a challenge due to competitive reactions in the dehydrogenation and/or condensation and great difficulty in ethanol dehydrogenation. This work reports a synergistic catalysis between layered double hydroxide (LDO), an acidic-basic support, and supported Ag particles for the dehydrogenation coupling of ethanol to n-butanol. A selectivity of up to 77% toward n-butanol with an ethanol conversion of 23.2%, among impressive levels reported till now, has been achieved at 350 degrees C, 0.1 MPa. A selectivity of up to 60% toward n-butanol with an ethanol conversion of 45%, the highest selectivity at an ethanol conversion of >45% reported till now, has been achieved at 250 degrees C, 2 MPa. A synergistic catalysis between the acid-base sites of the LDO surface and supported Ag particles have been revealed to contribute the excellent butanol selectivity: basic sites promote adsorption and subsequent dehydrogenation of ethanol on Ag particles; in addition to the promotion from Ag, the following aldol condensation is boosted by acid-base cooperation.