Cuphea section Amazoniana, one of 13 sections in Cuphea, comprises 20 species, mostly narrow endemics in Colombia, Ecuador, and the Guiana Shield region of Venezuela, Guyana, French Guiana, and Brazil. The species inhabit river margins, tepuis, scrubland, savanna, and low montane forests in tropical to cold temperate climates. They are subshrubs defined by the common presence of a strigose indumentum of bifid (malpighiaceous) trichomes; small elliptic to narrowly lanceolate or linear coriaceous leaves; and tubular flowers to 9 mm long with 11 deeply inserted stamens included in the floral tube. In morphology, they are similar to or partially overlap species currently classified in Cuphea sections Trispermum and Heteranthus. The revision provides a new key, comparative morphological descriptions, first descriptions and illustrations of pollen and seed morphology, and distribution maps. Cuphea saxatilis S. A. Graham, sp. nov. from Colombia and Cuphea trisperma S. A. Graham, sp. nov. from Venezuela are newly described. Cuphea killipii Lourteig is placed in synonomy of C. philombria Lourteig. Presence or absence of a floral spur, position and shape of a nectary-like floral organ, the “disc”, and presence of two major pollen types suggest the section is not monophyletic, but consists of a minimum of two phylogenetic lineages, one in the Guiana Shield region in Venezuela and eastward, the other in low montane forests and on outliers of the Guiana Shield in Colombia and northern Ecuador. Fossilized Cuphea pollen grains resembling two types of pollen known in sect. Amazoniana, establish the presence of the genus in theMio-Pliocene toHolocene of northern South America in areas occupied today by members of the section.