The mechanism of the electric-pulse induced resistance change effect in Au/Pr_0.65Ca_0.35MnO₃/SrTi_0.99Nb_0.01O₃ thin-film samples is studied by means of in situ electrical stimulation inside a transmission electron microscope. A detailed equivalent-circuit model analysis of the measured current–voltage characteristics provides crucial information for the proper interpretation of the microscopy results. The electrical transport data of the electron-transparent samples used for the in situ investigations is verified by comparison to measurements of unpatterned thin-film samples. We find comprehensive evidence for electrochemical oxygen vacancy migration affecting the potential barrier of the pn junction between Pr_0.65Ca_0.35MnO₃ and SrTi_0.99Nb_0.01O₃ as well as the resistance of the manganite bulk. The high-resistance state formation in the Pr_0.65Ca_0.35MnO₃ bulk is frequently accompanied by structural transformations, namely detwinning and superstructure formation, most likely as the result of the joint impact of dynamic charge inhomogenities by oxygen vacancy migration and injection of high carrier densities at the electrodes.