A worldwide surge in invasive Group A Streptococcal (GAS) infection has now been linked to the emergence of the novel M1UK lineage. Genomic screening of Australian invasive M1UK clinical isolates identified a mutation of A111V in CovR, a component of the CovRS two-component regulatory system. Normally, CovR (transcriptional regulator) dimerises upon phosphorylation by CovS (histidine kinase), driving transcriptional regulation of up to 15% of the GAS genome. Mutations in CovRS, or CovRS switching, have been implicated in the upregulation of several virulence factors in other GAS lineages (e.g. M1T1; a predecessor lineage to M1UK) resulting in a hypervirulent phenotype. Further genomic screening of clinical M1UK GAS isolates identified novel covRS mutations and revealed a comparable CovRS switching rate as observed for M1T1. In vitro, M1UK containing CovRA111V exhibit a hypervirulent phenotype similar to M1T1, characterised by decreased cysteine protease expression and increased expression of haemolytic toxins and hyaluronic acid capsule, promoting immune evasion. While the effect of CovRS switching on GAS virulence is well established, less is known about how CovR mutations affect protein function. We demonstrate an inability of recombinant CovRA111V to dimerise in a phosphorylation-dependent manner. In parallel, molecular dynamics simulations suggest that the A111V mutation specifically destabilises the interface between CovR monomers that facilitate dimerisation, inhibiting CovR dimer-mediated transcriptional repression of virulence genes and promoting a hypervirulent phenotype. Together, these data demonstrate further evidence of covRS switching in M1UK and provide insight into the structural basis for dysregulation of CovR during infection.