Fluorination is a common method to induce backbone planarity in semiconducting polymers via noncovalent interactions that effectively lock the rotation of single bonds along the backbone. Often explored in dry-state devices, fluorination of isoindigo polymer backbones in mixed conductors remains relatively unexplored. Herein, we investigated systematic fluorination of a family of isoindigo-based mixed conducting polymers with hybrid ethylene glycol-based side chains to probe the impact of fluorination on the resulting assembly and electrochemical performance. Through UV–Vis–NIR, FTIR, Raman spectroscopy, and electrochemical methods, we showed that fluorination effectively planarizes portions of the backbone depending on the fluorination location, even with ethylene glycol side chains, and the placement of fluorine atoms along the backbone is crucial toward organic electrochemical transistor (OECT) device performance. Electronic conduction was found to be improved upon fluorinating the isoindigo acceptor unit in OECTs, but it came at the cost of decreased volumetric ionic capacitance. Further, fluorinating the bithiophene donor inhibited p-type conduction in OECTs. As a result, systematic fluorination revealed the importance of understanding the nuanced design requirements of isoindigo-based mixed conductors for the optimal balance of both modes of conduction in aqueous environments.