We report the first experimental determination of the oxidation potentials Eox0 (relative to the standard hydrogen electrode, SHE) of model green fluorescent protein (GFP) chromophores. Para-, meta, and ortho-hydroxy (4-hydroxybenzylidene-2,3-dimethylimidazolinone, HBDI) and methoxy (MeOBDI) derivatives were studied. Eox0 of the three isomers in acetonitrile are -1.31, -1.52, and -1.39 V, respectively. Electronic structure calculations reproduce the observed differences between the isomers and reveal that Eox 0 follows the ionization energies (IEs), that is, p-MeOBDI has the lowest IE (6.96 eV in the gas phase) due to resonance stabilization of its cation, whereas the resonance is detuned in m-MeOBDI, resulting in more-negative Eox0. The observed meta and ortho effects in Eox0 are similar to the trends in pKa. The effect of increased solvent polarity on absolute Eox0 (and especially on para-meta-ortho differences) was found to be small. The redox properties of GFP chromophores are driven by their structure and can be correlated with IEs, which can be exploited in predicting the properties of other fluorescent protein chromophores.