This species is characterized by generally sparse strigillose to strigose puescence, medium-sized leaves, pedunculate inflorescnces that are congested to rather laxly cymose, medium-sized flowers, and subglobose fruits ca. 2 cm in diameter. This species locally common, and commonly collected, in much of its range. It is variable in leaf size and form, and degree of branching of the inflorescences. 

Guettarda macrosperma is similar to Guettarda subcapitata, and to Guettarda foliacea. A few plants from northwestern Costa Rica have leaves and inflorescences that lack bracts like Guettarda macrosperma, but the smaller hypanthia and more delicate-seeming and slender corollas of Guettarda foliacea, and may represent hybrids (e.g., Hammel & Pérez 23963).