Much controversy has occurred in the past few decades regarding the nature of the sources, the petrogenetic processes, and the tectonic regime(s) of the Jurassic magmatism within the Southeast China magmatic belt. This study aims to contribute to the discussion with mineral chemistry, and whole-rock element and Sr-Nd-Hf-Pb isotopic geochemical data from granitic rocks and microgranular mafic enclaves from Macao, where two discrete groups of I-type biotite granites have been identified (referred to as Macao Group I [MGI] and Macao Group II [MGII]). It is proposed that the granitic magmas were generated by partial melting of infracrustal medium- to high-K, basaltic Paleoproterozoic to Mesoproterozoic protoliths (Nd depleted mantle model age [TDM2] = 1.7–1.6 Ga and Hf TDM2 = 1.8–1.6 Ga), triggered by underplating of hot mantle-derived magmas in an extensional setting related to the foundering of a previously flat slab (paleo–Pacific plate) beneath the SE China continent. The main differences between the two groups of Macao granites are attributed to assimilation and fractional crystallization processes, during which upper-crustal Paleozoic metasediments were variably assimilated by MGI magmas. This is evidenced by an increase in initial 87Sr/86Sr ratios with degree of evolution, presence of metasedimentary enclaves, and high percentage of zircon xenocrysts with Paleozoic ages. In addition, other processes like late-stage fluid/melt interaction and magma mixing also left some imprints on granite compositions (rare earth element tetrad effect plus non–charge-and-radius-controlled behavior of trace elements and decoupling between different isotope systems, respectively). The distribution of isotopically distinct granites in SE China reflects the nature of the two Cathaysia crustal blocks juxtaposed along the Zhenghe-Dapu fault.