AbstractEncyclia comprises over 150 species of orchids that occupy mainly seasonally dry habitats in tropical and subtropical America and are usually restricted to one or a few ecoregions. To determine whether species found in the same or neighboring ecoregions are closely related, we sampled more than 50 taxa, with an emphasis on species found in Mexico and Central America. We evaluated five DNA markers for their phylogenetic utility: the nuclear low copy gene PHYC, a plastid spacer region trnL‐F, a fragment of the plastid ycf1 gene, rpl32‐trnL, and the internal transcribed spacer (ITS) region of nuclear ribosomal DNA; we sampled only the last three markers for the main analyses based on an assessment of phylogenetic informativeness. We analyzed plastid regions and ITS separately in phylogenetic inference using a variety of methods, as we found strong incongruence between them, according to the ILD test. We also estimated clade ages using a relaxed molecular clock with indirect calibrations based on a larger taxonomic sampling. Encyclia is a monophyletic genus that originated ca. 12.43 Ma (10.55–14.25 Ma) ago, and has undergone several recent evolutionary radiations. We found a strong association between phylogenetic relationships and the geographic distribution of species and clades in the Caribbean, Central American, and the Pacific coast of Megamexico. Several groups of Encyclia occur in the latter region, the most species‐rich being the E. meliosma complex, which is restricted to the Pacific slope of Mexico from north of the Isthmus of Tehuantepec up to Sonora.