CuO-based nanostructures have been widely investigated in catalysis, sensing, and energy conversion and storage in recent years. The unique properties of these nanostructures are largely related to the morphology and crystallinity of CuO. The controlled deposition of conformal CuO thin films by atomic layer deposition (ALD) has remained challenging until now owing to the limited understanding of the nucleation behavior and growth process. Here, a novel ALD process for copper oxide was developed using copper(II) trifluoroacetylacetonate [Cu(tfacac)2] as the metal precursor. The nucleation and initial growth of a CuO film are strongly dependent on the surface OH concentration. A continuous particulate-like CuO film was grown on OH-abundant pristine SiO2 particles, whereas the surface of the annealed SiO2 particles (presenting mostly isolated OH groups) remained uncoated under the same growth conditions. Moreover, a uniform and conformal CuO film was grown on covalently functionalized CNTs under identical conditions as pristine SiO2 particles. This study provides a strategy for tailoring the structure and the properties of thin films via ALD, which is promising for designing well-tailored nanostructures for various applications.