Streptomyces bacteria make numerous secondary metabolites, including half of all known antibiotics. Production is coordinated with their complex life cycles but the regulators that coordinate development with antibiotic biosynthesis are largely unknown. This is important to understand because most Streptomyces secondary metabolites are not produced under laboratory conditions and unlocking the cryptic biosynthetic gene clusters (BGCs) is a major focus for antibiotic discovery. Here we characterise the highly conserved actinobacterial response regulator MtrA in Streptomyces species. MtrA is essential and regulates cell cycle progression in Mycobacterium tuberculosis. We show that MtrA is also essential in Streptomyces venezuelae where it controls genes required for DNA replication and cell division. MtrA also directly regulates the expression of genes in >70% of its BGCs and artificially activating MtrA switches on the production of antibiotics in S. coelicolor and S. venezuelae. We propose that MtrA coordinates antibiotic production and development in Streptomyces species.