Understanding interfacial reactions that occur between the active layer and charge-transport layers can extend the stability of perovskite solar cells. In this study, the exposure of methylammonium lead iodide (CH₃NH₃PbI₃) thin films prepared on poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-coated glass to 70% relative humidity (R.H.) leads to a perovskite crystal structure change from tetragonal to cubic within 2 days. Interface-sensitive photoluminescence measurements indicate that the structural change originates at the PEDOT:PSS/perovskite interface. During exposure to 30% R.H., the same structural change occurs over a much longer time scale (>200 days), and a reflection consistent with the presence of (CH₃)₂NH₂PbI₃ is detected to coexist with the cubic phase by X-ray diffraction pattern. The authors propose that chemical interactions at the PEDOT:PSS/perovskite interface, facilitated by humidity, promote the formation of dimethylammonium, (CH₃)₂NH₂⁺. The partial A-site substitution of CH₃NH₃⁺ for (CH₃)₂NH₂⁺ to produce a cubic (CH₃NH₃)_1−x[(CH₃)₂NH₂]_xPbI₃ phase explains the structural change from tetragonal to cubic during short-term humidity exposure. When (CH₃)₂NH₂⁺ content exceeds its solubility limit in the perovskite during longer humidity exposures, a (CH₃)₂NH₂⁺-rich, hexagonal phase of (CH₃NH₃)_1−x[(CH₃)₂NH₂]_xPbI₃ emerges. These interfacial interactions may have consequences for device stability and performance beyond CH₃NH₃PbI₃ model systems and merit close attention from the perovskite research community.