Abstract Transitions from outcrossing to selfing and from diploidy to polyploidy often co-occur in plants, likely because the ability to produce selfed seed increases the likelihood of newly formed polyploids to become established. An ideal system to study these transitions is Primula, where the shift from diploid, outcrossing progenitors to polyploid, selfing descendants co-occurred repeatedly and the genetic basis of the mating-system shift is known. In Primula, outcrossing is enforced in distylous, typically diploid species characterized by florally heteromorphic, self-incompatible individuals, whereas selfing is enabled in homostylous, typically polyploid species, characterized by florally homomorphic populations of self-compatible plants. Distyly is controlled by the S-locus supergene. Small loss-of-function mutations in the S-locus CYPT gene, which controls style length and female self-incompatibility, are associated with loss of heterostyly in diploid, ancestrally heterostylous Primula species. However, CYPT and the S-locus have never been investigated in interspecific shifts from distylous, diploid species to homostylous, polyploid species. By analyzing the first assembled genome of a homostylous, polyploid species (Primula grandis) in a comparative framework, we discovered two, nearly identical S-locus alleles in the same subgenome, consistent with the hypothesis that the species originated from a cross between a homostylous, diploid pollen donor and a long-styled, diploid pollen recipient. Conformant to theoretical predictions, the macroevolutionary loss of distyly coincided with considerable degeneration of CYPT, including multiple mutations and exon loss, while other S-locus genes remained largely unaffected. This study advances knowledge on the macroevolutionary dynamics of supergenes and genomes in shifts between breeding systems and ploidy levels.