The marine actinomycete genus Salinispora is widespread in tropical marine sediments and possesses a great diversity of secondary metabolite biosynthetic pathways. In the present study, comparative genomics of 75 Salinispora strains confirm earlier observations that secondary metabolite pathways are significantly concentrated in genomic islands (GIs), whose boundaries are shown here to be conserved across all three Salinispora species. The GI that housed the greatest number of pathways varied among species and contained up to 40% of the pathways observed in a given strain. GIs were also significantly enriched in mobile genetic elements, including prophages and CRISPR phage defense systems, illustrating a constant gene flux in these regions. Whole-genome alignments underlined GIs as the major variable regions between strains, highlighting the importance of horizontal gene transfer for Salinispora diversification and functional adaptation. Furthermore, genomic rearrangements resulting in pathway "hopping" between islands or the exchange of specific pathway types at the same genomic site were observed. In many cases, pathway content was correlated with Salinispora taxonomic diversity, illustrated by a variety of phylotype- and subclade-specific pathways. In addition, several pathways were restricted to strains from certain geographic sites, suggesting a biogeographic influence to secondary metabolism. These observations shed light on genomic architecture and pathway distributions in a globally distributed group of marine bacteria and may prove valuable in the design of microbial drug discovery strategies.