Invertebrate and vertebrate GATA transcription factors play important roles in ectoderm and mesendoderm development, as well as in cardiovascular and blood cell fate specification. However, the assignment of evolutionarily conserved roles to GATA homologs requires a detailed framework of orthologous relationships. Although two distinct classes, GATA123 and GATA456, have been unambiguously recognized among deuterostome GATA genes, it has been difficult to resolve exact orthologous relationships among protostome homologs. Protostome GATA genes are often present in multiple copies within any one genome, and rapidly evolving gene sequences have obscured orthology among arthropod and nematode GATA homologs. In addition, a lack of taxonomic sampling has prevented a stepwise reconstruction of protostome GATA gene family evolution.We have identified the complete GATA complement (53 genes) from a diverse sampling of protostome genomes, including six arthropods, three lophotrochozoans, and two nematodes. Reciprocal best hit BLAST analysis suggested orthology of these GATA genes to either the ancestral bilaterian GATA123 or the GATA456 class. Using molecular phylogenetic analyses of gene sequences, together with conserved synteny and comparisons of intron/exon structure, we inferred the evolutionary relationships among these 53 protostome GATA homologs. In particular, we resolved the orthology and evolutionary birth order of all arthropod GATA homologs including the highly divergent Drosophila GATA genes.Our combined analyses confirm that all protostome GATA transcription factor genes are members of either the GATA123 or GATA456 class, and indicate that there have been multiple protostome-specific duplications of GATA456 homologs. Three GATA456 genes exhibit linkage in multiple protostome species, suggesting that this gene cluster arose by tandem duplications from an ancestral GATA456 gene. Within arthropods this GATA456 cluster appears orthologous and widely conserved. Furthermore, the intron/exon structures of the arthropod GATA456 orthologs suggest a distinct order of gene duplication events. At present, however, the evolutionary relationship to similarly linked GATA456 paralogs in lophotrochozoans remains unclear. Our study shows how sampling of additional genomic data, especially from less derived and interspersed protostome taxa, can be used to resolve the orthologous relationships within more divergent gene families.