N 6-methyladenosine (m6A) is the most prevalent modified nucleotide in mRNA 1,2 , with ~25% of mRNAs containing at least one m6A. Methylation of mRNA to form m6A is required for diverse cellular and physiological processes 3 . Although the presence of m6A in an mRNA can affect its fate in different ways, it is unclear how m6A directs this process and why the effects of m6A can vary in different cellular contexts. Here we show that the cytosolic m6A-binding proteins, YTHDF1–3, undergo liquid-liquid phase separation (LLPS) in vitro and in cells. This LLPS is markedly enhanced by mRNAs that contain multiple, but not single, m6A residues. Polymethylated mRNAs act as a multivalent scaffold for binding YTHDF proteins, juxtaposing their low-complexity domains, leading to phase separation. The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated compartments, such as P-bodies, stress granules, or neuronal RNA granules. m6A-mRNA is subject to compartment-specific regulation, including reduced mRNA stability and translation. These studies reveal that the number and distribution of m6A sites in cellular mRNAs can regulate and influence the composition of the phase-separated transcriptome. Additionally, these findings indicate that the cellular properties of m6A-modified mRNAs are governed by liquid-liquid phase separation principles.