Silicon-based materials serve as the core platform for the semiconductor industry, and elemental doping modification is a research hotspot for enhancing their carrier transport properties. In this study, the modulation mechanism of carrier mobility in three-dimensional silicon-based semiconductors doped with chalcogen elements (S, Se, Te) is systematically investigated by combining first-principles calculations with deformation potential theory, aiming to clarify the intrinsic correlation between dopant species and material transport performance. A substitutional doping model with a concentration of 1.56% is constructed. The structures are thoroughly optimized using density functional theory-based first-principles calculations, and the crystal structure and thermodynamic stability of each doped system at 300 K are verified. Within the framework of deformation potential theory, the evolution of the band structure under different strain conditions and along different crystallographic directions is analyzed, from which the electron effective mass, deformation potential constant, and elastic modulus are extracted. The electron mobility is then calculated using the Boltzmann transport equation and the relaxation time approximation. The results show that the S, Se, and Te substituted doping structures all exhibit good crystal structure and thermodynamic stability, forming stable doping configurations. The band structures of the doped systems show similar evolution trends along different crystallographic directions under four strain conditions, yet exhibit significant differences in deformation potential and effective mass in response to different dopant species. Among them, the Te-doped system shows the most stable deformation potential constant, consistently within the narrow range of 5.4–5.5 eV, along with the smallest effective mass. This results in an average electron mobility of 162.0 cm²/(V·s), which is significantly higher than those of the Se-doped (149.5 cm²/(V·s)) and S-doped (124.7 cm²/(V·s)) systems. The electron mobility exhibits a clear increasing trend with increasing atomic number of the chalcogen dopant, revealing the modulation behavior of chalcogen doping on the electron transport properties of silicon materials. This study provides theoretical guidance for the doping modification of silicon-based materials and the development of high-performance microelectronic devices.