Abstract: Whole-rock Sm-Nd and Rb-Sr isochron methods are important tools for low-temperature thermochronology. However, conventional whole-rock methods often fail to yield well-defined isochron ages due to the limited variation in Sm/Nd and Rb/Sr ratios during magmatic crystallization and differentiation. To overcome this limitation, this study developed a stepwise dissolution method combined with thermal ionization mass spectrometry (TIMS) to achieve high-precision internal isochron dating using a single rock sample. Different reagents—acetic acid, hydrochloric acid of various concentrations, aqua regia, and hydrofluoric acid—were sequentially used to dissolve a single granodiorite porphyry sample. The Sm-Nd and Rb-Sr isotopic compositions of each dissolved phase were measured by TIMS. The established method was then applied to the Chenzishan granodiorite porphyry in southeastern Hubei Province. Compared with whole-rock values, stepwise dissolution significantly amplified the variations in Sm/Nd and Rb/Sr ratios among the different fractions, enabling the construction of high-precision Sm-Nd and Rb-Sr mineral internal isochrons. The obtained Sm-Nd isochron age is 131.6 ± 2.8 Ma (MSWD = 1.3), and the Rb-Sr isochron age is 131.47 ± 0.34 Ma (MSWD = 0.73). These two ages are highly consistent with each other and also agree with the ages of volcanic rocks in the Jinniu Basin and the regional gold mineralization epoch. This single-sample dating method requires only a small amount of sample, is cost-effective, and effectively avoids age–isotope decoupling caused by uncertainties in sample ages from different spatial locations or uneven mineral distribution. The ～131 Ma age obtained for the Chenzishan granodiorite porphyry records a post-magmatic hydrothermal event and constrains the timing of the Chenzishan hydrothermal gold mineralization. This method provides a new approach for accurately determining the ages of low-temperature hydrothermal ore deposits.