Abstract: The Wusihe lead-zinc deposit, situated at the southwestern margin of the Yangtze Block and a prominent Ge-enriched deposit within the Sichuan—Yunnan—Guizhou lead-zinc metallogenic province, faces ongoing debates regarding its genesis. The influence of sphalerite typomorphic characteristics on Ge enrichment and substitution mechanisms within the deposit remains a crucial puzzle to unravel. To address this, our study employs quantitative analyses using microspectrophotometry and laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS). Results reveal the presence of two sphalerite stages during the hydrothermal period: a darker Stage I and a lighter Stage II. Despite similar mean values for visual reflectance and the dominant wavelength of reflectance color, the mean reflectance color saturation differs (0.048 and 0.043, respectively), with corresponding average Ge contents of 244×10⁻⁶ and 43.2×10⁻⁶. The experimental outcomes conclude that Ge exists in sphalerite as isomorphism and is more concentrated in sphalerite with higher reflectance color saturation. The substitution of Ge is related to Cu and Ag, with two stages of Ge⁴⁺+2Cu⁺ ↔ 3Zn²⁺, Ge⁴⁺+2 (Cu, Ag)⁺↔ 3Zn²⁺. The ore-forming temperature is medium to low, classifying the deposit as a Mississippi Valley-type lead-zinc deposit. The BRIEF REPORT is available for this paper at http://www.ykcs.ac.cn/en/article/doi/10.15898/j.ykcs.202406210138.