Garnet-bearing mafic granulite and amphibolite exposed as lenses, boudins, or interlayers within metasediments in the Qingshigou area, Dunhuang block, southernmost Central Asian orogenic belt, record important information for understanding the tectono-metamorphic evolution of subduction and collision zones in the southern Central Asian orogenic belt during the mid-Paleozoic. Three stages of metamorphic assemblages (M1, M2, M3) are recognized in the high- and medium-pressure mafic granulite and amphibolite. In the high-pressure mafic granulite, the prograde assemblage (M1) is represented by inclusion minerals (hornblende + plagioclase + quartz) preserved in garnet porphyroblasts; the metamorphic peak assemblage (M2) is characterized by garnet porphyroblasts and matrix minerals (garnet + clinopyroxene + plagioclase + quartz ± zircon ± titanite); and the retrograde assemblage (M3) is marked by coronitic symplectite (hornblende + plagioclase + quartz ± magnetite) rimming the garnet porphyroblasts. In the medium-pressure mafic granulite, the prograde assemblage (M1) of hornblende + plagioclase + quartz is included in the garnet porphyroblasts; the peak assemblage (M2) consists of garnet + orthopyroxene + clinopyroxene + plagioclase + quartz ± zircon ± titanite (M2) in the matrix; and the retrograde assemblage (M3) of hornblende + orthopyroxene + plagioclase + quartz (M3) surrounds the garnet porphyroblasts. In the amphibolite, the prograde assemblage (hornblende + plagioclase + quartz + ilmenite) is preserved as inclusions in garnet (M1); the peak assemblage (M2) is composed of garnet + hornblende + plagioclase + quartz ± zircon ± titanite; and the retrograde assemblage (M3), consisting of hornblende + biotite + plagioclase + quartz + epidote + magnetite, rings the garnet porphyroblasts. Geothermobarometric calculations suggest that the metamorphic pressure-temperature paths pass from 568 °C and 8.8 kbar through 607 °C and 10.6 kbar and 861 °C and 16.9 kbar and finally to 598 °C and 4.4 kbar for the high-pressure mafic granulite; from 756 °C and 9.0 kbar through 750–874 °C and 9.3–11.6 kbar to 675 °C and 4.7 kbar for the medium-pressure mafic granulite; and from 686 °C and 7.6 kbar through 715–766 °C and 10.6–11.2 kbar to 671 °C and 5.6 kbar for the amphibolite, and the paths show clockwise pressure-temperature loops typical of an orogenic process. The metamorphic peak of the high-pressure mafic granulite lies in the eclogite facies, which is indicative of a subduction zone environment. High-resolution secondary ion mass spectrometry (SIMS) U-Pb dating of metamorphic zircon indicates that the metamorphism occurred in the Early Silurian (ca. 430 Ma) and lasted for at least 65 m.y. This study reveals a possible southward subduction history of a branch of the Paleo–Asian Ocean, the Liuyuan Ocean, from the Silurian to Late Devonian, which may be an important event in the accretionary history of the Central Asian orogenic belt.