Magnetic field-induced changes in the electrical resistance of materials reveal insights into the fundamental properties governing their electronic and magnetic behavior. Various classes of magnetoresistance have been realized, including giant, colossal, and extraordinary magnetoresistance, each with distinct physical origins. In recent years, extreme magnetoresistance (XMR) has been observed in topological and non-topological materials displaying a non-saturating magnetoresistance reaching 103−108% in magnetic fields up to 60 T. XMR is often intimately linked to a gapless band structure with steep bands and charge compensation. Here, we show that a linear XMR of 80,000% at 15 T and 2 K emerges at the high-mobility interface between the large band-gap oxides γ-Al2O3 and SrTiO3. Despite the chemically and electronically very dissimilar environment, the temperature/field phase diagrams of γ-Al2O3/SrTiO3 bear a striking resemblance to XMR semimetals. By comparing magnetotransport, microscopic current imaging, and momentum-resolved band structures, we conclude that the XMR in γ-Al2O3/SrTiO3 is not strongly linked to the band structure, but arises from weak disorder enforcing a squeezed guiding center motion of electrons. We also present a dynamic XMR self-enhancement through an autonomous redistribution of quasi-mobile oxygen vacancies. Our findings shed new light on XMR and introduce tunability using dynamic defect engineering.