Angraecoid orchids present a remarkable diversity of chromosome numbers, which makes them a highly suitable system for exploring the impact of karyotypic changes on cladogenesis, diversification and morphological differentiation. We compiled an annotated cytotaxonomic checklist for 126 species of Angraecinae, which was utilised to reconstruct chromosomal evolution using a newly-produced, near-comprehensive phylogenetic tree that includes 245 angraecoid taxa. In tandem with this improved phylogenetic framework, using combined Bayesian, maximum likelihood and parsimony approaches on ITS-1 and five plastid markers, we propose a new cladistic nomenclature for the angraecoids, and we estimate a new timeframe for angraecoid radiation based on a secondary calibration, and calculate diversification rates using a Bayesian approach. Coincident divergence dates between clades with identical geographical distributions in the angraecoids and the pantropical orchid genus Bulbophyllum suggest that the same events may have intervened in the dispersal of these two epiphytic groups between Asia, continental Africa, Madagascar and the Neotropics. The major angraecoid lineages probably began to differentiate in the Middle Miocene, and most genera and species emerged respectively around the Late Miocene-Pliocene boundary and the Pleistocene. Ancestral state reconstruction using maximum likelihood estimation revealed an eventful karyotypic history dominated by descending dysploidy. Karyotypic shifts seem to have paralleled cladogenesis in continental tropical Africa, where approximately 90% of the species have descended from at least one inferred transition from n = 17–18 to n = 25 during the Middle Miocene Climatic Transition, followed by some clade-specific descending and ascending dysploidy from the Late Miocene to the Pleistocene. Conversely, detected polyploidy is restricted to a few species lineages mostly originating during the Pleistocene. No increases in net diversification could be related to chromosome number changes, and the apparent net diversification was found to be highest in Madagascar, where karyotypic stasis predominates. Finally, shifts in chromosome number appear to have paralleled the evolution of rostellum structure, leaflessness, and conspicuous changes in floral colour.