Metabolic flexibility is a common hallmark of aggressive and metastatic cancers. Here, we reveal that dynamic changes in mitochondrial translation rates drive the switch between glycolytic and mitochondrial energy production required for metastasis. We find that loss of 5-methylcytosine (m5C) in mitochondrial tRNAMet is sufficient to repress mitochondrial translation and trigger the switch from oxidative phosphorylation (OXPHOS) to glycolysis. Glycolytic tumour cells form primary tumours but fail to metastasize in an orthotopic mouse model of human oral cancer. Instead, a small subpopulation of non-dividing tumour cells requires high OXPHOS levels for invasion and metastasis. Although this metastasis-initiating metabolic switch is highly dynamic and reversible, we identify a mitochondria-driven gene signature predictive for lymph node metastasis and disease progression. Finally, we demonstrate that pharmacological inhibition of mitochondrial translation blocks metastasis in orthotopic transplants. Together, our results indicate that metastasis-initiating cells can be eradicated by blocking mitochondrial translation.