Vanadium slag is the primary source for vanadium extraction and also a source for chromium production owing to containing a considerable amount of chromium. However, it is challenging to extract vanadium and chromium in a green, safe, simple, and efficient way under ambient conditions. Here we report a facile process for simultaneous extraction of vanadium and chromium from vanadium slag via a mechanochemical activation–assisted microbubbles method. The vanadium slag subjected to mechanochemical activation exhibited markedly enhanced leaching efficiencies for both vanadium and chromium under atmospheric pressure compared to that of the slag that did not undergo mechanochemical activation. This enhancement in leaching efficiency can be primarily attributed to the synergistic effect of the mechanochemical treatment and microbubbles. The microbubbles enhance the generation of reactive oxygen species in an alkaline medium, while the mechanochemical activation process increases the utilization efficiency of these reactive oxygen species due to the improved interfacial reactivity of the vanadium slag. This study introduces a promising alternative for the environmentally responsible treatment of vanadium slag, showcasing a novel method for extracting vanadium and chromium through a mechanochemical activation-assisted microbubbles approach.