Objectives: Ongoing acquisition of antimicrobial resistance genes has made Morganella morganii a new clinical treatment challenge. Understanding the molecular epidemiology of M. morganii will contribute to clinical treatment and prevention. Methods: We undertook a 6-year clinical molecular epidemiological investigation of M. morganii from three tertiary hospitals in China since 2014. Antimicrobial susceptibility testing was performed using a VITEK-2 system. All isolates were screened for β-lactam and plasmid-mediated quinolone resistance genes by PCR. Isolates carrying carbapenem-resistant genes were subjected to whole-genome sequencing (WGS). The variation and evolution of these mobile genetic elements (MGEs) were then systematically analyzed. Results: Among all M. morganii isolates (n = 335), forty (11.9%) were recognized as multidrug resistant strains. qnrD1, aac(6')-Ib-cr, bla TEM-104, and bla CTX-M-162 were the top four most prevalent resistance genes. Notably, phylogenomic and population structure analysis suggested clade 1 (rhierBAPS SC3 and SC5) associated with multiple resistance genes seemed to be widely spread. WGS showed a bla OXA-181-carrying IncX3 plasmid and a Proteus genomic island 2 variant carrying bla CTX-M-3, aac(6')-Ib-cr coexisted in the same multidrug resistant strain zy_m28. Additionally, a bla IMP-1-carrying IncP-1β type plasmid was found in the strain nx_m63. Conclusion: This study indicates a clade of M. morganii is prone to acquire resistance genes, and multidrug resistant M. morganii are increasing by harboring a variety of MGEs including two newly discovered ones in the species. We should be vigilant that M. morganii may bring more extensive and challenging antimicrobial resistance issue.Copyright © 2021 Xiang, Lan, Cai, Liao, Zhao, Tao, Ma, Zeng, Zhang, Wu, Yu, Liu, Lu, Xu, Chen, Tang, Chen, Jia and Huang.