Volcanic-hosted iron deposits of the eastern Awulale metallogenetic belt in Central Asia possess a reserve of over 1.2 billion tons of iron ores and constitute one of the most important basements for high-grade iron resources in China. Skarns are widespread in these deposits and closely associated with iron mineralization. The ages of these skarns are unclear, and their genesis remains debated, preventing further investigation into their metallogenic processes. We focused on garnets in nine ore-bearing skarns from three large-scale iron deposits (Chagangnuoer, Dunde, and Beizhan) in the eastern Awulale belt. U-Pb dating was conducted on these garnets using our in-house reference material, the Taochong garnet (TC-13, Pb-Pb isochron age: 126.2 ± 2.3 Ma, initial 207Pb/206Pb ratio: 0.845 ± 0.022). Laser-ablation–multicollector–inductively coupled plasma–mass spectrometry (LA-MC-ICP-MS) was employed in the garnet U-Pb dating, and high-precision U-Pb ages (0.3%–1.6%) were obtained, highlighting the advantages of LA-MC-ICP-MS in dating low-U minerals. The garnet U-Pb ages of the nine skarn samples fall into three groups, i.e., 329.0 ± 5.1–326 ± 3.3 Ma (two samples), 316.3 ± 2.9–311.2 ± 2.4 Ma (six samples), and 295.6 ± 1.0 Ma (one sample), implying three episodes of skarn alteration in the volcanic-hosted iron mineralization system. The first and second episodes of skarns formed as a result of contact metasomatism between coeval volcanic rocks and limestone, and they have economically important iron mineralization. The third was likely caused by a local postcollision granitic intrusion, but its metallogenic potential deserves further assessment.