Late Ordovician (ca. 451 Ma) calc-alkaline adakitic granodiorite and granite, associated with coeval S-type granites, were discovered in the Central Tianshan block, NW China. They are characterized by high Sr (526–620 ppm), but low Y (6.8–8.6 ppm) and heavy rare earth element (HREE) contents (e.g., Yb = 0.7–0.8 ppm), and thus have high Sr/Y (66–86) ratios. The granodiorite has SiO2 of 69.3 wt%, MgO of 1.4 wt%, and Mg# of 48, exhibiting light (L) REE–enriched patterns ([La/Yb]N = 15.82, [Dy/Yb]N = 1.25) with strong positive Eu (δEu = 1.65) but weak negative Nb, Ta, and Ti anomalies. Its low Cr (9.0 ppm) and Ni (6.2 ppm) concentrations, low negative εHf(t) and εNd(t) values (–11.3 to –5.0 and –4.8, respectively), old one-stage Nd model age (ca. 1.4 Ga), and high initial 87Sr/86Sr ratio (0.7129) are characteristics of derivation from the partial melting of thickened ancient lower crust, most likely in the eclogite facies. The adakitic granite samples contain slightly higher SiO2 (72.4–73.0 wt%), but lower MgO (0.6–0.7 wt%) and Mg# (37–40), with low Cr (7.9–12.1 ppm) and Ni (5.6–7.4 ppm), displaying concave-upward REE patterns ([La/Yb]N = 19.25–30.01, [Dy/Yb]N = 0.85–1.01) with negligible Eu (δEu = 0.87–1.03) and pronounced negative Nb, Ta, and Ti anomalies. Their positive εHf(t) (+4.3 to +7.1) and εNd(t) (+1.6 to +3.2) values, young one-stage Nd model ages (0.9–0.8 Ga), and low initial 87Sr/86Sr ratios (0.7055–0.7060) indicate generation by the partial melting of relatively juvenile lower crust, probably in the garnet-bearing amphibolite facies. Combined with previous investigations, we suggest that the Central Tianshan developed as a continental arc along northern Tarim, facing the southward subduction of the Junggar oceanic plate during Ordovician time. Lower-crustal melting was likely induced by asthenosphere upwelling in response to rollback of the Junggar oceanic slab, accompanied by crustal extension and incipient opening of the South Tianshan back-arc basin along northern Tarim and separation of the Central Tianshan as a microcontinent. The heat brought by the ascending adakitic magmas possibly caused anatexis of the basement rocks, forming the coeval pelite-derived S-type granites. The eastern segment of the South Tianshan Ocean was most probably closed prior to ca. 380 Ma. This study provides ample evidence that adakitic rocks can be produced by partial melting of (thickened) lower crust during incipient opening of a back-arc basin.