To better understand the occurrence and succession of antibiotic resistance genes (ARGs) in the environment, the investigation of ARGs in sediment for a long time scale is urgently needed. In this study, sediment samples were taken in the Yangtze Estuarine area from 2007 to 2019, and the interannual variations in ARGs and their possible physicochemical and socioeconomic influencing factors were analyzed. The results showed that the abundance of ARGs, including sul1, sul2, tetM, tetW, aac(6′)-Ib and qnrS, was higher in recent years (from 2015 to 2019) than that in earlier years (from 2007 to 2011), and heavier ARG pollution was found in Wusongkou (WSK) samples than in Liuhekou (LHK) samples. According to the redundancy discriminant analysis (RDA) and correlation analysis, the antibiotics (especially individual antibiotic categories, including oxytetracycline, doxycycline hyclate and norfloxacin), metals and a metal resistance gene (zntA) and total organic carbon (TOC) showed significant correlations to ARGs. In addition, antibiotics, metals, TOC and ARGs were also significantly correlated with several socioeconomic indices. Furthermore, the extended STIRPAT model analysis revealed that the second industry product and the first industry product were the major socioeconomic driver factors for the ARG distribution at WSK and LHK, respectively. Overall, with socioeconomic development, antibiotics, metals, TOC and ARGs increased in sediment. In addition, antibiotics, metals and TOC may participate in the regulation of the occurrence and distribution of ARGs in the Yangtze Estuary for the long time scale.