The mechanisms and processes underlying patterns of species distributions have intrigued ecologists and biogeographers for a long time. The Neotropics is the most species-rich region in the World, representing an excellent model for studying the drivers of diversification. In this study, we used a phylogenomic approach to infer relationships and examine the role of major geological and climatic events in shaping biogeographic patterns within Amphilophium (Bignonieae, Bignoniaceae), a genus of Neotropical lianas. Even though Amphilophium is broadly distributed across the Neotropics, it is centered in Amazonia and the Atlantic rainforest. We generated nearly-complete plastome sequences for 32 species of Amphilophium, representing 70% of the species diversity in the genus. The final dataset included 78 plastid-coding regions and was analyzed under Maximum Likelihood and Bayesian approaches to reconstruct the phylogeny of Amphilophium. We also used this dataset to estimate divergence times using a Bayesian relaxed-clock approach. We further inferred ancestral ranges, migration events, and shifts in diversification rates using a branch-specific diversification model and the Dispersal-Extinction-Cladogenesis (DEC) model implemented in a Bayesian phylogenetic framework. Overall, we obtained a well-resolved and strongly supported phylogeny for Amphilophium, with five main clades that are well characterized by morphological features. Amphilophium originated in the Early Oligocene, and started to diversify in the Late Oligocene. The first diversification event involved a split between Amazonian and Atlantic forest clades. These two clades showed very different diversification scenarios. Divergence within the Atlantic forest clade began in the Mid-Oligocene, while the Amazonian clade underwent rapid diversification starting in the Late Miocene. In-situ speciation characterized the Amazonian clade, whereas allopatric speciation driven by migration events into other Neotropical biomes were mostly inferred within the Atlantic forest clade. The diversification of Amphilophium in the Neotropics was triggered by major geological events and changes in landscape that occurred during the Late Paleogene and Neogene, with little influence of the climatic changes of the Pleistocene ice ages. The divergence times and range inferences support the role of the Western Amazonian “megawetlands” and the formation of the South American “dry diagonal” as key climatic and geological barriers that separated the Atlantic forest from the Amazonian lowlands. Timing of migration events agrees with a Mid-Miocene closure of the Central American Seaway.