Towards developing next generation scalable TiO2-based resistive switching (RS) memory devices, the efficacy of 50 keV Ar+-ion irradiation to achieve self-organized nano-channel based structures at a threshold fluence of 5 × 1016 ions/cm2 at ambient temperature is presented. Although x-ray diffraction results suggest the amorphization of as-grown TiO2 layers, detailed transmission electron microscopy study reveals fluence-dependent evolution of voids and eventual formation of self-organized nano-channels between them. Moreover, gradual increase of TiO/Ti2O3 in the near surface region, as monitored by x-ray photoelectron spectroscopy, establishes the upsurge in oxygen deficient centers. The impact of structural and chemical modification on local RS behavior has also been investigated by current-voltage measurements in conductive atomic force microscopy, while memory application is manifested by fabricating Pt/TiO2/Pt/Ti/SiO2/Si devices. Finally, the underlying mechanism of our experimental results has been analyzed and discussed in the light of oxygen vacancy migration through nano-channels.