The Meghalaya Plateau including the Mikir Hills represents the northeastern extension of the Precambrian Indian Shield and mainly comprises the Proterozoic basement granite gneisses, granites (sensu lato), granulites, metasediments, Cambrian granites, and Mesozoic‐Tertiary lithounits. A new whole‐ rock geochemical dataset of Proterozoic and Cambrian granites is presented and investigated to decipher the petrogenesis of these granites with its implications on understanding the crustal growth history of Meghalaya Plateau. Cambrian granites commonly intrude the Proterozoic basement granite gneisses and Shillong Group of rocks. Both the Proterozoic and Cambrian granites exhibit similar mineral assemblages (Bt ± Amp‐Pl‐Kf‐Qz‐Zrn‐Mag‐Ttn‐Ap ± Ilm), but they are texturally distinct. Microgranular enclaves are ubiquitous in Cambrian plutons but are devoid or rare in the Proterozoic granites. Cambrian granites are medium‐ to coarse‐grained, inequigranular, hypidiomorphic, frequently porphyritic, and undeformed to mildly deformed, whereas Proterozoic granites are medium‐ to coarse‐grained, less frequent porphyritic, and mildly to strongly deformed. Geochemically, the Proterozoic (molar Al2O3/CaO + Na2O + K2O (A/CNK) = 0.86–1.15; FeOt/FeOt + MgO = 0.60–0.93) and Cambrian (A/CNK = 0.77–1.20; FeOt/FeOt + MgO = 0.56–0.90) granites are nearly identical showing strongly metaluminous to moderate peraluminous, magnesian to ferroan, and alkali‐calcic to calc‐alkaline and transitional character between I‐type and A‐type oxidized granites formed in a post‐collision tectonic environment. Comparison of studied granites with experimental melt compositions derived from various protoliths suggests that they are sourced from metabasics to tonalites. Harker bivariate plots demonstrate fractional differentiation as a dominant process in the evolution of these granites. However, occurrence of hybrid microgranular enclaves and geochemical features manifest that the mixing and fractionation of coeval mafic and felsic magmas have also played a key role in the evolution of some Cambrian plutons. A slightly higher zircon saturation temperatures for Cambrian (700–950°C) than the Proterozoic (675–900°C) granites characterize a relatively higher‐T melting regime for the generation of Cambrian than the Proterozoic granites. Petrogenetic modelling constrains that the parental magma to the Proterozoic granites can be generated by about 25.5% melting of heterogeneous lower crustal sources with low maficity, which subsequently had undergone fractional crystallization involving bt‐amp‐pl‐Kf‐qz assemblage. However, parental to Cambrian granites can be produced by about 32% melting of the amphibolitic lower crust that subsequently evolved through synchronous fractional crystallization and mixing with a mantle‐derived mafic melt. The chronological records and the present petrogenetic findings on Proterozoic granites propound a viable geodynamic model that the assembly and growth (thickening) of the Columbia Supercontinent during ca. 1,800–1,600 Ma caused a hi...