In this work, we study the effects of microscopic shape, crystallinity, and purity for the chemical reaction of CuO nanoparticles with hydrogen sulfide (H2S) to form copper sulfide. Several CuO nanomaterials were prepared via various synthesis techniques, including sol-gel, precipitation, hydrothermal synthesis in the presence of a polymer/surfactant, hydrolysis, and electrospinning, using different copper precursors (nitrate and acetate) and thermal treatment conditions (623-1023 K). The synthesized materials, which had different morphologies (flowerlike, nanobelt-like, petallike, spherical, and nanofibers) and physiochemical chemical properties (e.g., crystallite size, surface area, and pore volume), were tested for their performance as low-temperature H2S sorbents in fixed-bed experiments at 294 K and 1 atm. Despite ostensible differences between the various properties of the tested sorbents, a strong linear relationship was recognized between the sorbents' sulfur removal capacity and crystallite size, independent of changes in the materials' microscopic shape and porosity. Specifically, it was observed that CuO materials with crystallite sizes larger than 26 nm exhibited low sulfur uptake capacities (less than 0.5 wt %), whereas capacity increased linearly (from 0.5 to 12 wt %) with decreasing crystallite sizes for materials with CuO crystallites from 26 to 5 nm. In addition, the effect of residual carbon on CuO surfaces was also probed in this study, for the first time, showing that amorphous carbon inherently imparted by the use of a polymer, poly(vinylpyrrolidone) (PVP) or poly(ethylene oxide) (PEO), or a surfactant, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123), in the synthesis procedure inhibits reaction and deleteriously impacts the H2S uptake capacity. This trend demonstrates that sorption capacity is strongly influenced by crystallite size and is independent of microscopic shape, surface area, and mesopore structure. First-principles atomistic simulations explain which surface O anions are most reactive and supportive to the observations.