Surface modification of metal oxide nanostructures with noble metals has attracted significant attention of researchers because of their importance in gas sensing applications. In this regard, mesoporous zinc oxide nanospheres (ZnO NSs) were designed through a simple template-free solvothermal approach and successive anchoring of gold nanoparticles (Au NPs) onto it was achieved through a chemical process followed by thermal treatment. The synergistic effects of different Au NPs loadings onto the structure, surface morphology, element contents, as well as chemiresistive gas sensing activities of solvothermal-mediated ZnO NSs were examined thoroughly and discussed. Gas sensing studies demonstrated that the sensor based on Au@ZnO-3 NSs exhibits excellent acetone (CH3COCH3) sensing characteristics (Response = 194) compared to pristine ZnO NSs sensor (Response = 2.86) at a lower temperature of 170 °C. Besides, Au@ZnO NSs sensor is able to detect CH3COCH3 concentration down to ppb-levels (500 ppb) with excellent response repeatability. Observed CH3COCH3 sensing performances of all the Au loaded ZnO NSs sensors were found to be almost 50 times higher than pristine ZnO NSs sensor. Such an excellent CH3COCH3 sensing performance of Au@ZnO NSs is mainly credited to the catalytic activity of Au NPs and the strong metal-semiconductor contacts between Au NPs and ZnO NSs.