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The growing antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious global threat to gonococcal therapy. Molecular typing is an ideal tool to reveal the association between specific genotype and resistance phenotype that provides effective data for tracking the transmission of resistant clones of N. gonorrhoeae In our study, we aimed to describe the molecular epidemiology of AMR and the distribution of resistance-associated genotypes in Shenzhen during 2014-2018. In total, 909 isolates were collected from Shenzhen from 2014-2018. Two typing schemes, multilocus sequence typing (MLST) and N. gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR), were performed for all isolates. The distribution of resistance-associated genotypes was described using goeBURST analysis combined with data of logistic regression. Among 909 isolates, ST 8123 , ST 7363 , ST 1901 , ST 7365 , and ST 7360 were most the common MLST sequence types (STs), and ST 348 , ST 2473 , ST 497 , and ST 199 were the most prevalent NG-STAR STs. The logistic regression analysis showed that NG-STAR ST497 , MLST ST7365 , and MLST ST7360 were typically associated with decreased susceptibility to ceftriaxone. Furthermore, the internationally spreading ESC-resistant clone MLST ST1901 has been prevalent at least in 2014 in Shenzhen and showed a significant increase during 2014-2018. Additionally, MLST ST7363 owns the potential to become the next internationally spreading ceftriaxone-resistant ST. In conclusions, we performed a comprehensive epidemiological study to explore the correlation between AMR and specific STs, which provided important data for future studies of the molecular epidemiology of AMR in N. gonorrhoeae Besides, these findings provide insight for adjusting surveillance strategies and therapy management in Shenzhen., (Copyright © 2021 American Society for Microbiology.)