Human modifications of stream systems often result in channel instability and sediment pulse- induced problems. While previous research explored the direct anthropogenic impacts of channelization on fluvial systems, the history of repeated channelization, their persistent impacts on headwater streams and subsequent evolution of a drainage system need further investigation. This study evaluates the spatial distribution of channel form and stability in Big Barren Creek watershed, which drains the karst dominated Ozark Highlands of southeast Missouri. The objectives of this research are threefold: (i) describe channel morphology and hydrology in undisturbed and disturbed segments based on field data, (ii) propose a conceptual model of channel modification and response to explain the patterns of channel adjustment and (iii) evaluate the history of channel disturbance using historical aerial photograph analysis. Results show that disturbed reaches have larger channel dimensions than undisturbed reaches because channelization increased stream power and shear stress, particularly for channels that are actively incising. Channelized reaches are primarily identified on private land where headcuts developed and migrated upstream to the national forestland. Sediment supply to the channel increases from both upstream incision and bank and levee collapse resulting in downstream aggradation, which forces landowners to repeat channelization for flood control. The proposed conceptual model suggests that while the disturbed segments evolve into wider and deeper channels following channelization, they exhibit the potential to become stable over time because of biogeomorphic resistance (e.g., in-channel vegetation, armored-cohesive soil) related to the ephemeral nature of the streams in this karst region. This idea is also supported by the slower average headcut migration rate of earlier channelization (2 m/yr) compared to recent channelization (6–8 m/yr). However, channel adjustment largely depends on repeated channelization that resets the evolutionary stages that preclude this fluvial system from attaining stability.