To promote the development and application of MgO-based one-part alkali-activated slag materials (AASM), MgO and sodium silicate were used as activators by the ways of single or combined to study their effects on hydration microstructure and mechanical properties of one-part AASM. Moreover, micro-mechanical properties were also analyzed by nanoindentation. Results showed that the formation of Mg(OH)2 after MgO contacted with water provided an alkaline environment, which induced the dissolution of slag. While the dissolution of sodium silicate further elevated the solution pH and accelerated the fracture of Al-O and Si-O chemical bond as well as the released of Ca2+. This formed a double strengthening effect to promote the hydration of slag. In addition, the composite activator of MgO and sodium silicate produced more abundant hydration products. Pore structure analysis revealed that AASM had the lowest porosity and the least harmful pores by using the combined MgO and sodium silicate to activate slag. More hydration products with high elastic modulus were produced in combination with MgO and sodium silicate, thus contributing to the increase in micro-mechanical properties.