AbstractThe electronic structure of constituent layers and the spin channel of propagating electrons are critical factors that affect the magnitude and sign of magnetoresistance (MR) in synthetic antiferromagnets (SAFMs), which are important for spintronic applications. However, for all‐oxide‐based SAFMs, where there is strong coupling between multiple degrees of freedom, spin transport becomes more complex and remains elusive. Here, using ultrathin half‐metallic manganite/doped ruthenate SAFMs as a model system, three sign reversals of MR are demonstrated accompanied by the crossover between underlying spin‐dependent transport mechanisms. Electron tunneling produces normal MR in the current‐perpendicular‐to‐plane (CPP) geometry at low temperatures, whereas carrier confinement causes inverse MR in the current‐in‐plane (CIP) geometry. Strikingly, CPP MR can undergo a temperature‐driven sign reversal due to resonant tunneling via localized states in the spacer. Moreover, hydrostatic pressure can modulate the interlayer exchange coupling and induce an asymmetric interfacial response to dramatically facilitate electron tunneling, driving a controllable sign reversal of CIP MR. These results provide new insights into understanding and optimization of MR in all‐oxide‐based SAFMs.