Copper-based catalysts are highly promising for electrochemical CO2 reduction to value-added products, but they face the challenges of high potential and low products selectivity. Herein, CuS catalysts with different Cu/S ratios were prepared via the hydrothermal synthesis method, and the morphology and structure of the catalysts were characterized by XRD, FESEM, and XPS, to investigate the effect of sulfur content on their “structure-reactivity” relationships in CO2 reduction. Results indicated that sulfur content affected the nucleation and growth of CuS crystals, which in turn exerted impacts on the morphology and sulfur vacancy defects of the catalysts. As the Cu/S ratio varied from 2:1 to 1:4, surface morphology of the catalysts changed from the lotus shape to ball-flower structure, and the concentration of sulfur vacancies increased from 20.66% to 63.37%, which resulted in the significant enhancement of CO2 reduction activity and CO selectivity. The optimum Cu/S ratio was 1:4, and the desired CuS-1:4 catalyst exhibited a high CO selectivity of 72.67% under a mild potential of -0.51 V (reversible hydrogen electrode RHE) in 0.1 M KHCO3 electrolyte. The excellent CO2 reduction performance was associated with the expanded surface area and extended gas diffusion channels provided by the ball-flower structure and the facilitated electron transfer and strengthened adsorption of the *COOH intermediates on the catalyst surface contributed by the abundant sulfur vacancy defects.