North Carolina's river drainages continue to lose their faunal distinctiveness as nonnative fish species establish themselves and expand their distributions, resulting in biotic homogenization. One such example is the Pee Dee drainage on the Atlantic Slope. It is the most speciose drainage in North Carolina, inhabited by 113 species of which 34 are nonindigenous, many introduced from adjacent drainages. The history of fish investigations in the Pee Dee in North Carolina and Virginia is detailed herein. The fauna was first sampled by Cope in 1869 at two conjoined sites—Yadkin River and Gobble Creek, a small tributary at the Yadkin River site (Cope 1870). Cope described numerous new taxa from the drainage, and many subsequent researchers provided data that show additions of nonnative faunal elements. As a case study, indications are that Hypentelium roanokense, Roanoke Hog Sucker, Hypentelium nigricans, Northern Hog Sucker, and Moxostoma rupiscartes, Striped Jumprock, were cryptically introduced after the late 1950s. The Roanoke Hog Sucker, introduced as recently as the 2000s, is found only in three tributaries of the Ararat subsystem in North Carolina and Virginia. The Northern Hog Sucker has expanded its range very little, confined primarily to the North Fork Reddies and Ararat subsystems and a short segment of the mainstem Yadkin River in North Carolina. The Striped Jumprock is now in much of the upper Yadkin system, but not in Virginia, and at several sites in the South Yadkin subsystem. Natural dispersal of all three species is limited by dams and impoundments, but the dispersal by Striped Jumprock has probably been aided by multiple bait bucket introductions. Consequences of nonindigenous species introductions in the drainage are well known for some species but unknown for the Roanoke Hog Sucker, Northern Hog Sucker, and Striped Jumprock.