The limited selectivity of existing CO2 reduction catalysts and rising levels of CO2 in the atmosphere necessitate the identification of specific structure-reactivity relationships to inform catalyst development. Herein, we develop a predictive framework to tune the selectivity of CO2 reduction on Cu by examining a series of polymeric and molecular modifiers. We find that protic species enhance selectivity for H-2, hydrophilic species enhance formic acid formation, and cationic hydrophobic species enhance CO selectivity. ReaxFF reactive molecular dynamics simulations indicate that the hydrophilic/hydrophobic modifiers influence the formation of surface hydrides, which yield formic acid or H-2. These observations offer insights into how these modifiers influence catalytic behavior at the non-precious Cu surface and may aid in the future implementation of organic structures in CO2 reduction devices.