Author summary Plasmids are extrachromosomal elements that disseminate antimicrobial resistance (AMR) among bacteria. Neisseria gonorrhoeae is a leading cause of sexually transmitted disease and a concern due to increasing AMR. It contains a restricted repertoire of plasmids, including a conjugative plasmid, pConj, which disseminates plasmid-mediated AMR. We show that, in contrast to broad host range plasmids, pConj is largely restricted to and adapted to N. gonorrhoeae, and has been remarkably conserved since it first emerged over 80 years ago. pConj is highly persistent, with no plasmid loss detected after 160 generations under standard laboratory conditions. We were unable to identify any chromosomal gene to account for the success of pConj. Instead, the lack of fitness costs and co-operative effects of maintenance systems result in its stable inheritance. Of note, pConj harbours an orphan VapD toxin that can be neutralised by VapX antitoxins expressed by a co-resident plasmid; this potential ‘split’ toxin:antitoxin system allows exquisite association of pConj with the gonococcus. Finally, we show that ciprofloxacin can induce pConj loss, mirroring the reduction in pConj carriage in the gonococcal population following introduction of this antibiotic for gonorrhoea, and paving the way for approaches to eliminate plasmid-mediated AMR in this important human pathogen.