The Panaque nigrolineatus group (subgenus Panaque) is revised; three nominal species—P. cochliodon, P. nigrolineatus, and P. suttonorum—are redescribed and three new species are described. Panaque armbrusteri, new species, is widespread in the Tapajós River and its tributaries in Brazil and is distinguished by having a supraoccipital hump, higher numbers of jaw teeth and an ontogenetic increase in interpremaxillary and intermandibular tooth-row angles, relatively short paired-fin spines, and dorsal margin of infraorbital six flared laterally. Panaque schaeferi, new species, is widespread in main-channel habitats of the upper Amazon (Solimões) River basin in Brazil and Peru; it is distinguished by having a coloration consisting of dark or faded black spots evenly distributed on a pale gray to brown base, and by its large adult body size (>570 mm SL). Panaque titan, new species, is distributed in larger, lowland to piedmont rivers of the Napo River basin in Ecuador, and is distinguished by having a postorbital pterotic region bulged beyond the ventral pterotic margin, coloration consisting of irregular and widely spaced dark gray to brown stripes on light brown to tan base, and large adult body size (>390 mm SL). A relatively large pterotic, indicative of an enlarged gas bladder and gas bladder capsule, and allometric increases in tooth number are hypothesized to be synapomorphies uniting members of the subgenus Panaque.