Many marine sponges host diverse symbiotic microbial communities that have been implicated in the production of secondary metabolites. These metabolites may defend the host sponge from potential predators. Variability in symbiont communities across the range of the host sponge could alter levels of chemical defense. To investigate the relationship between symbiont composition and chemical defense, the microbiomes and palatability of tissue samples from Ircinia campana were characterized from 5 sites along a latitudinal gradient spanning temperate (South Atlantic Bight, SAB) and tropical (Caribbean) regions. Terminal restriction fragment length polymorphism analysis and Illumina sequencing of 16S ribosomal RNA genes revealed that I. campana from different locations contained significantly distinct microbiomes and exhibited a consistent relationship of lower symbiont similarity over greater geographic distance (i.e. distance-decay). However, crude organic extracts of all samples of I. campana were unpalatable to assay fish Thalassoma bifasciatum in laboratory assays, indicating no difference in chemical defense across locations. Distinct haplotypes of I. campana were detected in populations from the SAB and Caribbean, correlating with the observed patterns of latitudinal variation in microbial symbiont communities. Our findings indicate that I. campana is chemically defended from fish predators across the range of the species and that latitudinal variation occurs in the microbiome of I. campana, driven by a combination of host-specific factors and region-specific environmental filtering of symbiont communities.