Shigellosis is an enteric infection that transmits through the faecal-oral route, which can occur during sex between men who have sex with men (MSM). Between 2009 and 2014, an epidemic of sexually transmissible Shigella flexneri 3a occurred in England that subsequently declined. However, from 2018 to 2021, despite restrictions to control SARS-CoV-2 spread, S. flexneri 3a re-emerged. We explored possible drivers of the re-emergence by comparing host demographic features and pathogen genomics. The age and geographical distribution of cases in 2009–2014 (relative to 2018–2020) was comparable, with cases primarily among 35–64 year old men in London and the Southeast, a majority (54%) of which self-identified as gay or bisexual. Genomic analyses of 502 bacterial isolates showed that the majority (58%) of re-emerging MSM strains were a clonal replacement of the original lineage, with a reduced antimicrobial resistance profile. Specifically, more recent isolates had lost blaTEM−1 and erm(B), likely in line with shifting antimicrobial selection pressures. The absence of major changes in the pathogen or host demographics suggest that other factors, such as host immunity, may have driven the re-emergence of S. flexneri 3a and highlight the need for further work in the area.