Highlights•Phase and microstructure evolutions of Mo2FeB2-based cermets with the temperatures were explored.•Tribology and wear behaviors of the cermets were studied.•The tribo-oxide layer simultaneously reduced the CoF and wear rate at 400 °C and 600 °C.•Load and temperature were crucial to the formation and stability of tribo-oxide layer.During the sintering process, the phase evolution of Mo2FeB2-based cermets mainly occurred in the solid stage. When the liquid formed, the phase composition remained constant and the “dissolution-reprecipitation” process predominated the microstructural evolution. At 1250 °C, the hardness, transverse rupture strength and fracture toughness of Mo2FeB2-based cermets reached 88.6 HRA, 1480 MPa and 14.1 MPa⋅m1/2, respectively. The tribology and wear behaviors of Mo2FeB2-based cermets were evaluated from 25 °C to 800 °C. The abrasive wear prevailed at 25 °C, while the wear mechanism transitioned to oxidative mild wear due to the formation of the tribo-oxide layer at 400 °C and 600 °C. Besides the anti-wear Fe2O3, the lubricant MoO3 and B2O3 were also formed. The multi-component self-lubricating tribo-oxide layer simultaneously reduced the wear rate and coefficient of friction of Mo2FeB2-based cermets. However, by further increasing the temperature to 800 °C, the cracked matrix and impaired tribo-oxide layer resulted in the transition of wear mechanism to oxidative severe wear. The appropriate combination of load and temperature was necessary for the formation and stability of the tribo-oxide layer.