Complex oxides provide rich physics related to ionic defects. For the proper tuning of functionalities in oxide heterostructures, it is highly desired to develop fast, effective, and low‐temperature routes for the dynamic modification of defect concentration and distribution. Herein, the use of helium implantation to efficiently control the vacancy profiles in epitaxial La0.7Sr0.3MnO3−δ thin films is reported. The viability of this approach is supported by lattice expansion in the out‐of‐plane lattice direction and dramatic change in physical properties, i.e., a transition from ferromagnetic metallic to antiferromagnetic insulating. In particular, a significant increase of resistivity up to four orders of magnitude is evidenced at room temperature, upon implantation of highly energetic He ions. The result offers an attractive means for tuning the emergent physical properties of oxide thin films via strong coupling between strain, defects, and valence.