Indium (In), one of the strategic critical metal elements, is preferred to be enriched in the skarn system, but the enrichment regularity in terms of temporal and spatial distribution in a specific skarn Pb-Zn deposit remains unclear. To address the problem, we conducted a systematic geological, mineralogical, and trace element geochemical investigation on the Baoshan In-rich Pb-Zn polymetallic deposit, Hunan Province. This deposit is situated in the central part of the famous Nanling W-Sn-Pb-Zn polymetallic metallogeny belt, South China. Three ore districts in the Baoshan deposit with distinct economic element associations are divided, including the Central District (dominated by Cu-Mo), West District (dominated by Pb-Zn), and North District (dominated by Pb-Zn). They comprise a typical skarn system, including the outcropped granodiorite porphyry, typical skarn mineral assemblages, and Pb-Zn-hosting Carboniferous limestone. We systematically sampled the representative Pb-Zn ores in two ore districts (West and North) and three underground levels (-270 m, −230 m, and −190 m). Four types of sphalerites with different mineral associations and mineralogical characteristics were identified, that is, Sp1a and Sp1b (formed in the early sulfide stage), as well as Sp2a and Sp2b (formed in the late sulfide stage). Our EPMA (Electron Probe Micro-Analyzer) and LA-ICP-MS (Laser Ablation Inductively Coupled Plasma Mass Spectrometer) analyses reveal the four types of sphalerite have distinct chemical compositions. Such as, the mean value of indium is 3524 ppm for Sp1a, 142 ppm for Sp1b, 48.03 ppm for Sp2a, and 87.98 ppm for Sp2b in a decreasing order, and a similar trend of calculated temperatures ranging from 336 to 135 °C using GGIMFis thermometers can be obtained. Further LA-ICP-MS trace elements mapping show that the core of Sp1a is relatively enriched in more In, Cu, Sn, and Ag contents. Spatially, the sphalerites in the deep contain a higher indium content (mean = 1581 ppm) than those in the shallow (107.20 ppm) in the vertical profile. In the planar, indium is more enriched in the West District (mean = 1090 ppm) than in the North District (60.92 ppm). The indium distribution regularity reflects that the metals-carrying magmatic hydrothermal fluids flow from Central District, through the West District, to the North District. Collectively, we conclude that indium prefers to be enriched in the earlier stages, higher temperature, and deeper space during the sphalerite crystallization in the Baoshan skarn system, and therefore highlight the deep space of Baoshan West District is a promising target for indium exploration. This new finding maybe shed light on the scientific understanding on indium enrichment and associated exploration strategies in the similar skarn Pb-Zn metallogenic systems.