A series of drilling, dredge, and seismic investigations indicate that Mesozoic sediments exist in the South China Sea (SCS) which shows a bright prospect for oil and gas exploration. In order to study the distribution of Mesozoic strata and their residual thicknesses in the SCS, we carried out an integrated geophysical study based mainly on gravity data, gravity basement depth and distribution of residual Mesozoic thickness in the SCS were obtained using gravity inversion constrained with high-precision drilling and seismic data. In addition, the fine deep crustal structures and distribution characteristics of Mesozoic thicknesses of three typical profiles were obtained by gravity fitting inversion. Mesozoic strata in the SCS are mainly distributed in the south and north continental margins, and have been reformed by the later tectonic activities. They extend in NE-trending stripes are macro-controlled by the deep and large NE-trending faults, and cut by the NW-trending faults which were active in later times. The offset in NW direction of Mesozoic strata in Nansha area of the southern margin are more obvious as compared to the north margin. In the Pearl River Mouth Basin and Southwest Taiwan Basin of the north continental margin the Mesozoic sediments are continuously distributed with a relatively large thickness. In the Nansha area of the south margin the Mesozoic strata are discontinuous and their thicknesses vary considerably. According to the characteristics of Mesozoic thickness distribution and hydrocarbon potential analyses from drilling and other data, Dongsha Uplift-Chaoshan Depression, Southwest Taiwan Basin-Peikang Uplift and Liyue Bank have large thickness of the Mesozoic residual strata, have good hydrocarbon genesis capability and complete source–reservoir–cap combinations, show a bright prospect of Mesozoic oil/gas resources.