For decades, semiconductors and their heterostructures have underpinned both fundamental and applied research across all areas of electronics. Two-dimensional, 2D (atomically thin) semiconductors have now the potential to push further the miniaturization of electronic components, enabling the development of more efficient electronics. Here, we report on a large tunneling magnetoresistance of 1100% at a bias current of 1 nA and a giant anomalous zero-bias spin voltage effect in magnetic tunnel junctions based on 2D materials. The generation, manipulation and detection of electron spin across a nanometer-thick magnetic tunnel junction do not require any applied bias. The large zero-bias spin voltage signal exceeds 30,000%, which is far greater than the highest magnetoresistance signals reported to date. This non-equilibrium spin-engine state arises from the asymmetric diffusion of spin-up/spin-down electrons across the junction. It is driven by the built-in electric field of the junction and occurs under continuous energy exchange of the junction with the environment. Our findings reveal unexplored opportunities to transform and amplify spin information for low-power electronics.