The cause of across-arc geochemical and isotopic variations above subduction zone is still controversial. The researches on petrogenesis of arc-type mafic intrusive rocks may give important insights into the cause of the variations. Here we undertakes an integrated study of U–Pb zircon dating, geochemical and Sr–Nd–Hf isotopic compositions for the rear-arc (Keqianyakou and Jinyuan plutons) and arc-front mafic intrusive rocks (Liushendong and Yishenchun plutons) in the southern Central Qilian block. These mafic rocks have magma crystallization ages of 454–465 Ma. Their evolved Sr–Nd–Hf isotopic compositions and relatively low Ba/Th, Sr/Th and high La/Sm ratios indicate that they were derived from mantle sources modified by slab sediment melt. Compared to the rear-arc mafic rocks ((87Sr/86Sr)i = 0.7046–0.7054, εNd(t) = +0.8 to +2.4 and εHf(t) = +8.4 to +11.9), the arc-front mafic rocks are more enriched in strongly incompatible elements and have more evolved Sr–Nd–Hf isotopic compositions ((87Sr/86Sr)i = 0.7092–0.7116, εNd(t) = −4.3 to −5.4 and εHf(t) = −1.2 to −0.1). Sr–Nd and Nd–Hf two-endmember (depleted mantle and slab sediment melt) mixing models reveal that ~0.7% slab sediment melt was incorporated into the magma sources of the mafic rocks in the rear arc, while up to 4.5% was incorporated into those in the arc front. This difference probably reflects release of hydrous fluid from the slab, which contributed to fluid-fluxed melting of the slab sediment. In response to the decreasing involvement of slab sediment melt with depth, degree of partial melting (F) of the modified mantle decreases across the arc (i.e. F = 9% in the arc front and F = 5% in the rear arc). The results indicate that the extent of slab sediment melting and the degree of partial melting of the mantle wedge can account for the across-arc geochemical and isotopic variations of arc-type mafic rocks. We thus suggest that the northward subduction of the South Qilian (North Qaidam–West Qinling) Ocean (a branch of the Proto-Tethys Ocean) is responsible for the Early Paleozoic arc-type mafic magmatism at the southern Central Qilian block.