Aberrant accumulation of the metabolite D-2-hydroxyglutarate promotes certain types of cancers, but much uncertainty remains regarding which specific cellular processes are impacted by the oncometabolite to promote tumor growth. The structures of α-ketoglutarate and D-2-hydroxyglutarate are sufficiently similar that D-2-hydroxyglutarate can act as a competitive inhibitor of α-ketoglutarate-dependent enzymes both in vitro and in vivo. Several key epigenetic regulators, including members of the TET family of DNA demethylases and Jumonji histone demethylases, are among the known enzymes inhibited by D-2-hydroxyglutarate. Separating the effects of DNA and histone hypermethylation has been a challenge to the field. Saccharomyces cerevisiae naturally lacks DNA methylation machinery and thus provides a unique opportunity to study exclusively the effect of D-2-hydroxyglutarate accumulation on histone demethylation. Here, we have demonstrated that mutations analogous to those that cause D-2-hydroxyglutarate accumulation in human tumors recapitulated the effect in yeast. We have additionally uncovered a novel pathway for naturally producing and degrading D-2-hydroxyglutarate in yeast. Through a combination of genetic and molecular analyses, we found that D-2-hydroxyglutarate accumulation increased silencing of genes within heterochromatin. This effect was specifically mediated through D-2-hydroxyglutarate-inhibition of histone demethylase enzymes specific for H3K36 methyl marks. Our work has uncovered a mechanism by which the impact of D-2-hydroxyglutarate is leveraged by disrupting a widespread epigenetic regulatory process that leads to altered chromatin states and transcription. Inspired by these results we have expanded our study and uncovered multiple unexpected nodes in metabolism that impact heterochromatin stability, which will be discussed.