A single-step deposition of cobalt-doped zinc oxide (Co-ZnO) thin film nano-composites on three different crystalline substrates, viz., Al2O3 (c-sapphire), silicon (100) (Si), and SiO2 (quartz) is reported, using pulsed electron beam ablation (PEBA). The results indicate that the type of substrate has no effect on Co-ZnO films stoichiometry, morphology, microstructure, and film thickness. The findings show the presence of hexagonal close-packed metallic Co whose content increases in the films deposited on Al2O3 and Si substrates relatively to SiO2 substrate. The potential of the films as model nano-catalysts has been evaluated in the context of the Fischer-Tropsch (FT) process. Fuel fractions, which have been observed in FT liquid products, are rich in diesel and waxes. Specifically, Co-ZnO/Al2O3 nano-catalyst shows a selectivity of approximate to 4%, 31%, and 65% towards gasoline, diesel, and waxes, respectively, while Co-ZnO/SiO2 nano-catalyst shows a selectivity of approximate to 12%, 51%, and 37%, for gasoline, diesel, and waxes, respectively. (c) 2018 American Institute of Chemical Engineers AIChE J, 64: 3332-3340, 2018