γ‐valerolactone　(GVL)　is　a　key　value‐added　chemical　catalytically　produced　from　levulinic　acid　(LA),　an　important　biomass　derivative　platform　chemical.　Here　an　ultra‐efficient　3D　Ru　catalyst　generated　by　in　situ　reduction　of　RuZnOx　nanoboxes　is　reported;　the　catalyst　features　a　well‐defined　structure　of　highly　dispersed　in　situ　oxide‐derived　Ru　(IOD‐Ru)　clusters　(≈1 nm　in　size)　spatially　confined　within　the　3D　nanocages　with　rich　mesopores,　which　guarantees　a　maximized　atom　utilization　with　a　high　exposure　of　Ru　active　sites　as　well　as　a　3D　accessibility　for　substrate　molecules.　The　IOD‐Ru　exhibits　ultrahigh　performance　for　the　hydrogenation　of　LA　into　GVL　with　a　record‐breaking　turnover　frequency　(TOF)　up　to　59400　h−1,　14　times　higher　than　that　of　the　ex　situ　reduction　of　RuZnOx　nanoboxes　catalyst.　Structural　characterizations　and　theoretical　calculations　collectively　indicate　that　the　defect‐rich　and　coordination‐unsaturated　IOD‐Ru　sites　can　boost　the　activation　of　the　carbonyl　group　in　LA　with　a　significantly　lowered　energy　barrier　of　hydrogenation.