Harvest regulations are important for fishes that are both commercially and recreationally sought after such as Channel catfish (Ictalurus punctatus) throughout the Middle Mississippi River. Monitoring total harvest and understanding Channel catfish population dynamics (i.e., recruitment, growth, and mortality) are crucial for managing a sustainable population. Total commercial harvest and current harvest regulations in the Middle Mississippi River have not recently been evaluated. Thus, we evaluated total commercial harvest reports from 1945–2012 along with commercial fishing effort, population dynamics for the Middle Mississippi River Channel catfish population, and simulated the effects of various length limits on the reproductive potential and yield per recruit of the Channel catfish population. Overall, total commercial harvest has drastically declined from 1990–2012, while commercial effort has remained relatively constant. We speculate overexploitation as a possible cause to the decline in harvest given relatively constant commercial fishing effort. We collected 501 Channel catfish from the Middle Mississippi River during spring, summer, and fall of 2012–2013. Channel catfish were weighed, measured, aged (via lapilli otoliths), and egg samples were collected for fecundity estimates to obtain population level information. We used the static form of the spawning potential ratio (SPR) and the yield per recruit model to simulate variable exploitation rates at three different length limits (e.g., 356 mm, 381 mm, and 406 mm). Our yield per recruit simulation modeling results identified that a 381 mm length limit would not lead to growth overfishing until exploitation rates were between ~50 and 70%. Furthermore, simulation modeling predicted that the SPR was not below a critical minimum conservative threshold of 20% until exploitation rates reached between 50 and 70%; therefore, the population appears to be sustainable under the current length limit of 381 mm, if exploitation rates do not exceed 50–70%.