AbstractAn anisotropic double exchange interaction driven giant transport anisotropy is demonstrated in a canonic double exchange system of La_2/3Sr_1/3MnO₃ ultrathin films epitaxially grown on NdGaO₃ (110) substrates. The oxygen octahedral coupling at the La_2/3Sr_1/3MnO₃/NdGaO₃ interface induces a planar anisotropic Mn-O-Mn bond bending, which causes a significant anisotropic overlap of neighboring Mn orbitals. Due to the anisotropic double exchange interaction, it is found that the conductivity of the La_2/3Sr_1/3MnO₃ film is enhanced when current is applied along the in-plane short crystalline axis. However, the anisotropic behavior is absent in the high temperature paramagnetic phase. Our results demonstrate anisotropic transport in the clean limit where phase separation is absent and the role of anisotropic phase percolation can be excluded.