A new species, Drymonia quadrangulata Clavijo & J.L.Clark, sp. nov. (Gesneriaceae, Columneinae), is described from the western Andean slopes of southern Colombia and northern Ecuador. The new species has been historically confused with D. killipii, an endemic species to Colombia, restricted to the lowlands of the Chocó biogeographic region in the departments of Cauca, Chocó, and Valle del Cauca. These two species have large foliaceous calyx lobes that cover at least half of the corolla tube, and tubular-infundibuliform corollas. The new species differs by strigose quadrangulate and sometimes winged stems, leaves reticulate abaxially with obtuse to subcordate bases, midveins green, corolla lobes white to yellow with margins incised to short laciniate, and indehiscent berry fruits. Digital photographs, detailed morphological comparisons with the similar species, and an IUCN preliminary risk extinction assessment are provided for the new species.