Pseudomonas aeruginosa is a human opportunistic pathogen consisting of three phylogroups (hereafter named A, B, and C) of unevenly distributed size. Here, we assessed phylogroup-specific evolutionary dynamics in a collection of publicly available and newly sequenced genomes of P. aeruginosa. We explored to what extent antimicrobial resistance (AMR) genes, defence systems, and virulence genes vary in their distribution across regions of genome plasticity (RGPs) and “masked” (RGP-free) genomes, and to what extent this variation differs among the phylogroups. We found that members of phylogroup B possess larger genomes, contribute a comparatively larger number of gene families to the pangenome, but show lower abundance of CRISPR-Cas systems. Furthermore, AMR and defence systems are pervasive in RGPs and integrative and conjugative/mobilizable elements (ICEs/IMEs) from phylogroups A and B, and the abundance of these two types of cargo genes is often significantly correlated. Moreover, multiple inter- and intra-phylogroup interaction events occur at the accessory genome content level, suggesting that recombination events are frequent. Finally, we provide here a panel of phylogenetically diverse P. aeruginosa strains that can be used as a reference set for future functional analyses. Altogether, our results highlight distinct pangenome characteristics of the three phylogroups of P. aeruginosa, that are possibly influenced by variation in the abundance of CRISPR-Cas systems and that are shaped by the differential distribution of AMR and other defence systems.