This species is characterized by its extensively vining habit, its ovate to lanceolate, shortly petiolate leaves, its solitary flowers that are showy and borne on well developed peduncles, its rather well developed calyx lobes about 3-10 mm long, and its well developed, bright red, funnelform corollas with tubes 30-45 mm long and shorter lobes, 4-6 mm long. The corollas are distinctive in bud, when they are swollen and obovoid with top broadly rounded to truncate. The fruiting peduncles are often flexed in their upper part to hold the fruits erect even though the stem is pendulous. Manettia cordifolia is common in secondary vegetation and widely distributed, from the central Amazon basin to Argentina. This is one of the most commonly encountered and collected species in the genus. In general aspect this species in flower resembles some plants of Scrophulariaceae, Lobeliaceae, and Gesneriaceae and it is sometimes confused with those families.

Manettia cordifolia has some morphological variation across its range, and some infraspecific taxa have been named and some populations may deserve evaluation as to whether they are better considered separate species. The species shows variation in calyx lobe length and shape, corolla size, fruit size, and peduncle length, as well as some variation in leaf size. Several varieties of this species have been formally named, based on mainly details of pubescence, leaf shape, and petiole length, and some of these have been recognized by subsequent authors. However considering the geographic and ecological range it occupies, Manettia cordifolia could be considered actually to include rather little variation.

Schumann (1889) treated this species under the name Manettia ignita (Vell.) K. Schum., based on the name Guagnebina ignita Vell. which he considered an older name for this species (he mis-spelled it there as "Guangnebina"). He cited the name Manettia cordifolia as a synonym of his Manettia ignita and explicitly included Martius's type within his circumscription of Manettia ignita. However the name Manettia cordifolia was actually published before Vellozo's name, and thus has priority over it. Therefore Schumann's name Manettia ignita is incorrect (but not illegitimate; Art. 52.3). Schumann (1889) circumscribed Manettia cordifolia broadly, and synonymized 9 other species names. He surveyed this species across its range, and recognized 5 varieties. Chung (1968: pp. 357-363, fig. 10-16) again studied this species across its range, and recognized 4 varieties and 2 forms. He separated these based on the degree of lobing of the calyx limb, shape of the stem cross-section, and various details of pubescence. A majority of the plants of this species belonged to his Manettia cordifolia var. cordifolia, which was widely distributed. Most of Chung's infraspecific taxa have coherent geographic ranges, though these ranges largely overlap. Chung also detailed a number of specimens that were intermediate morphologically and not classified to an infraspecific taxon.