Geochronological, geochemical, and Sr–Nd isotope data for the mafic rocks from Cuona and Zhegucuo areas, Southern Tibet are presented to understand better the connection between the Kerguelen mantle plume and the breakup of eastern Gondwana. Zircon U–Pb dating yielded a concordant, weighted-mean 206Pb/238U age of 131 Ma for the Zhegucuo diabases. Compared to the Cuona basalts, the Zhegucuo diabases have higher Mg# values and MgO, Ni, and Cr contents closer to those of primary mantle melts. The Cuona basalts have ocean island basalt-like compositions, including light rare-earth element enrichments, positive Nb–Ta anomalies, and positive εNd(t) values (+1.20 to +2.97). The Zhegucuo diabases are characterized by Nb depletion, Zr and Hf enrichment, and negative εNd(t) values (−2.71 to −2.26). Modeling implies that low degrees (4––7%) of partial melting of garnet lherzolites (3–5 % garnet) within the Kerguelen mantle plume can produce Cuona basalts. However, the Zhegucuo diabases were formed by similar degrees (4–7%) of partial melting of spinel-bearing lherzolite (2 vol% spinel) in the shallow enriched lithospheric mantle. The positive anomalies of Zr–Hf in the Zhegucuo diabases are because their sources have melted. The Tethyan Himalaya underwent lithospheric thinning during the Early Cretaceous, resulting from the impact of the Kerguelen mantle plume. The breakup of eastern Gondwana could have been a combination of the reactivation of the former suture zone and the arrival of a new mantle plume beneath the Tethyan Himalaya.