Otocinclus macrospilus is one of the larger and more robustly built members of the genus, reaching up to 4.5 cm. It is distinguished by a strong, well-defined dark lateral stripe running from the snout through the eye to the base of the caudal fin, where it typically terminates in a dark blotch. This species is distributed across a wide range of South American drainages and is occasionally encountered in the aquarium trade alongside the more common O. affinis and O. vittatus.
In nature, O. macrospilus inhabits clear to lightly turbid rivers and streams with moderate current, where it congregates in schools over shallow, algae-rich substrate. Like all Otocinclus, it is a grazing specialist that feeds primarily on periphyton and soft algae, using its rasping mouthparts to harvest the thin biofilm coating leaves, rocks, and wood. It occupies a crucial ecological role as a primary consumer in these productive shallow-water habitats.
In the aquarium, O. macrospilus adapts well once past the initial acclimatisation period, which can be stressful for wild-caught individuals. It thrives in groups within planted aquaria with ample light to support algae growth, smooth decor for grazing, and gentle filtration. Its slightly larger size makes it marginally more robust than some of its congeners, which may ease transition from wild conditions.