The Central Canyon sandstones, located in the Ledong–Lingshui Depression, Qiongdongnan Basin, South China Sea, are the main reservoirs of the deep-water area. The present study aimed to examine the diagenetic processes and reservoir quality of these sandstones. Using an integrated approach of examination of casting thin sections, X-ray diffraction, porosity and permeability measurements, scanning electron microscopy, carbon and oxygen stable isotope analyses, fluid inclusion analyses and electron microprobe analysis, we analysed the diagenetic features of the sandstones and the reservoir quality of the LD30-1 and LS17-2 sandstones, respectively. The results showed that the sandstones consist of lithic arkoses and sublitharenites, the main pore systems consist of primary intergranular pores and secondary pores, and the main cements consist of authigenic quartz, clay minerals, and carbonates. By combining the analyses of burial history and hydrocarbon charging history, we discovered that the LD30-1 sandstone reservoirs and the LS17-2 sandstone reservoirs are quite different. A significant negative shift in δ13C and δ18O (ranging from −4.88‰ to −2.27‰ and from −11.83‰ to −5.96‰, respectively) is evident in the carbonate cements of the LD30-1 sandstones, and oxidation of organic matter had an important role in the occurrence of the carbonate cements. However, relatively high and concentrated δ13C and δ18O values in the LS17-2 sandstones, ranging from −1.76‰ to −0.48‰ and −5.04‰ to −2.95‰, respectively, are closer to the original isotopic compositions. Based on casting thin sections, the abundance of quartz overgrowths in the LD30-1 sandstones is higher than that in the LS17-2 sandstones. The development of each clay mineral in the LD30-1 and LS17-2 sandstones is quite different. The LS17-2 sandstones have higher reservoir quality than the LD30-1 sandstones. Early hydrocarbon charge is an important factor causing the differences of diagenetic minerals and reservoir quality between the LS17-2 sandstones and the LD30-1 sandstones.