Lichens are composite, symbiotic associations of fungi, algae, and bacteria that result in large, anatomically complex organisms adapted to many of the world’s most challenging environments. How such intricate, self-replicating lichen architectures develop from simple microbial components remains unknown because of their recalcitrance to experimental manipulation. Here, we report a metagenomic and metatranscriptomic analysis of the lichen Xanthoria parietina at different developmental stages. We identified 168 genomes of symbionts and lichen-associated microbes across the sampled thalli, including representatives of green algae, three different classes of fungi, and 14 bacterial phyla. By analyzing the occurrence of individual species across lichen thalli from diverse environments, we defined both substrate-specific and core microbial components of the lichen. Metatranscriptomic analysis of the principal fungal symbiont from three different developmental stages of a lichen, compared with axenically grown fungus, revealed differential gene expression profiles indicative of lichen-specific transporter functions, specific cell signaling, transcriptional regulation, and secondary metabolic capacity. Putative immunity-related proteins and lichen-specific structurally conserved secreted proteins resembling fungal pathogen effectors were also identified, consistent with a role for immunity modulation in lichen morphogenesis.