This study provides an analysis of vesicomyid bivalve–symbiont community distribution across cold seep and hydrothermal vent areas in the Guaymas Basin (Gulf of California, Mexico). Using a combination of morphological and molecular approaches including fluorescent in situ hybridization (FISH), and electronic microscopy observations, vesicomyid clam species and their associated symbionts were characterized and results were analyzed in light of geochemical conditions and other on‐site observations. A greater diversity of vesicomyids was found at cold seep areas, where three different species were present (Phreagena soyoae [syn. kilmeri], Archivesica gigas, and Calyptogena pacifica). In contrast, A. gigas was the only species sampled across the hydrothermal vent area. The same haplotype of A. gigas was found in both hydrothermal vent and cold seep areas, highlighting possible contemporary exchanges among neighboring vents and seeps. In either ecosystem, molecular characterization of the symbionts confirmed the specificity between symbionts and hosts and supported the hypothesis of a predominantly vertical transmission. In addition, patterns of clams could reflect potential niche preferences for each species. The occurrence of numerous traces of vesicomyid movements on sediments in the sites colonized by A. gigas seemed to indicate that this species might have a better ability to move. Furthermore, variation in gill sulfur content could reveal a higher plasticity and sulfur storage capacity in A. gigas. Thus, the distribution of vesicomyid species across the chemosynthetic areas of the Guaymas Basin could be explained by differences in biological traits of the vesicomyid species that would allow A. gigas to more easily exploit transient and punctual sources of available sulfide than P. soyoae.