The previous studies revealed the I‐type Ladakh magmatism in the Andean‐type southern margin of the Ladakh batholith (LB) was related to the subduction of the Neotethyan Ocean and India‐Eurasia collision. However, LB's S‐type granitic magmatism and associated mafic microgranular enclaves (MMEs) are poorly constrained. Here, we present the new data for S‐type Ladakh granite (LG) and associated monzodiorite MMEs in the Andean‐type orogeny in the southern margin of the Eurasian plate. The low SiO2 (47.4–53.9 wt%), high K2O (1.56–3.21 wt%), Mg# (52–65), continental‐arc tracer patterns, and slightly depleted to evolved Sr‐Nd isotopic composition ((87Sr/86Sr)i = 0.7047–0.7166; ℇNd (t = 50 Ma) = (+1.40 to −8.92)) for MME suggest that they were derived from the phlogopite‐bearing deep lithospheric mantle‐source at a depth of 5.4–10.5 km depth with 810–870°C, 1.4–2.8 kbar, and enriched by sediment‐melts addition into the mantle‐wedge from subducting Neotethyan Oceanic slab. The mantle‐derived ascending hot mafic magma mixing with felsic magma of the ancient northern Indian margin‐derived, generates monzodiorite MME by assimilation and magma mixing processes. Plagioclase, amphibole, and biotite chemistry support the magma mixing processes. LG are characterized by high SiO2 (63.4–75.0 wt%), K2O (3.93–5.67 wt%), CaO/Na2O ratio of >0.3, differentiation index (90.27–97.46), normative corundum (1.0–2.8), A/CNK values (1.00–1.18), hypersthene (0.7–5.7), and low Al2O3, MgO, TiO2, Fe2O3. They also exhibit peraluminous, variable tracer elemental abundances, variable (87Sr/86Sr)i ratios (0.6967–0.7191), and high whole rock ℇNd (t = 50 Ma) values of −4.15 to −11.92) and ancient two‐stage Nd model age of 1160 and 1858 Ma. These features suggest that S‐type Ladakh granites were derived from the melting of ancient metagreywacke‐dominated metasedimentary rocks of the northern Indian margin by a large amount of mafic magma underplating after subducted Neotethyan slab‐rollback. The formation of LG and MMEs related to the Andean‐type orogeny in the southern margin of the Eurasian plate.