How functional diversification affects the organization of the transcriptome is a central question in systems genetics. To explore this issue, we sequenced all six Odorant binding protein (Obp) genes located on the X chromosome, four of which occur as a cluster, in 219 inbred wild-derived lines of Drosophila melanogaster and tested for associations between genetic and phenotypic variation at the organismal and transcriptional level. We observed polymorphisms in Obp8a, Obp19a, Obp19b, and Obp19c associated with variation in olfactory responses and polymorphisms in Obp19d associated with variation in life span. We inferred the transcriptional context, or "niche," of each gene by identifying expression polymorphisms where genetic variation in these Obp genes was associated with variation in expression of transcripts genetically correlated to each Obp gene. All six Obp genes occupied a distinct transcriptional niche. Gene ontology enrichment analysis revealed associations of different Obp transcriptional niches with olfactory behavior, synaptic transmission, detection of signals regulating tissue development and apoptosis, postmating behavior and oviposition, and nutrient sensing. Our results show that diversification of the Obp family has organized distinct transcriptional niches that reflect their acquisition of additional functions.