The Cuonadong Dome in southern Tibet is a newly discovered gneiss dome in the Tethys Himalaya. Here, we investigate the Late Cambrian augen gneiss (orthogneiss) within the core of this dome to address the controversy surrounding early Palaeozoic tectonic evolution of the northern margin of eastern Gondwana. We report new zircon laser ablation multicollector inductively coupled plasma mass spectrometry (LA‐(MC‐)ICP‐MS) U‐Pb ages, Lu‐Hf isotopes, whole‐rock major and trace element geochemistry, and Sr‐Nd‐Pb data on representative samples from the granitic gneiss. The weighted mean of 116 analyses of zircon grains yields an age of 498.2 ± 1.5 Ma (mean square weighted deviation [MSWD] = 1.2). Forty‐one spots analyses on these grains show consistent εHf (t) values of −2 to +4 (average = +1.1), corresponding to Hf crustal model age (TDM2) of 1.3 to 1.6 Ga (average = 1.39 Ga). The orthogneiss (metagranite) is characterized by high Si and K contents, with low Al, Mg, and Ti, and A/CNK values ranging from 0.87 to 0.98 with an average of 0.92, indicating a metaluminous composition and I‐type granitoid affinity. The granitoid displays significant enrichment in light rare earth elements (LREEs) and relatively flat high rare earth element (HREE) patterns, with strong negative Eu anomalies (Eu/Eu* = 0.26–0.31). The primitive mantle‐normalized trace elements show a relative enrichment in large‐ion lithophile elements, such as Rb, and high‐field strength elements, such as Th, U, Zr, and Hf, with depletion in Ba, Nb, Ta, Sr, P, and Ti. The rocks show high initial 87Sr/86Sr ratios (0.7221–0.7248) and low εNd (t) values (−8.9 to −7.3) with Nd model ages (TDM) of 1.79–1.91 Ga. Their radiogenic Pb isotopic compositions show (206Pb/204Pb)t = 18.804–19.110, (207Pb/204Pb)t = 15.730–15.768, and (208Pb/204Pb)t = 38.409–39.054, indicating an ancient upper middle continental crustal origin. Our study shows that the protolith of the metagranite was most likely derived from the partial melting of upper continental crust with a minor contribution of depleted mantle materials. Through integration of the regional information on early Palaeozoic magmatism and metamorphic events, we contend that the protolith of the Cuonadong granitic gneiss formed in an accretionary setting associated with the early Palaeozoic Proto‐Tethys Oceanic plate subduction beneath the Gondwana continent.