We evaluated fish abundance trends in the non-tidal Potomac River of eastern North America and applied life history theory to interpret temporal trends. Data were collected by Maryland Department of Natural Resources personnel at 10 locations upstream from Great Falls over 43 years (1975-2017). Linear mixed models revealed significant temporal changes in abundance for 13 of the 28 species in the analysis. Increasing species were characterized by opportunistic life history strategies (i.e., small-bodied species with rapid maturity; e.g., banded killifish [Fundulus diaphanus]), whereas decreasing species were characterized by periodic or equilibrium strategies (i.e., large-bodied species that delay reproduction to invest in growth or parental care; e.g., smallmouth bass [Micropterus dolomieu]). Most increasing species are native to the study area and therefore probably do not indicate recent introductions. Results indicated that river flows during spawning have become less stable and less predictable over time, consistent with observed increases in spring peak-flows as well as predictions from land-use and climate change research.