Saccharomyces cerevisiae, widely used in industrial fermentation, still suffers from inherent problems in the efficient utilization of carbon sources. Here, a strategy for alleviating glucose effect and improving S-adenosyl-L-methionine (SAM) production by deleting Mig1 combined with introducing MetK1 from Leishmania infantum was applied in S. cerevisiae. The deletion of Mig1 improved glucose utilization by increasing the expression levels of genes related to glucose transport and glycolysis, thereby increasing the levels of glycolytic intermediates and increasing both the transcriptional levels of ACS1 and ALD6 and the activity of ADH2, which promotes the conversion of ethanol into acetyl-CoA. The deletion of Mig1 also upregulated the transcripts of genes involved in the metabolism of precursor amino acids of SAM and ultimately responsible for the improvement in SAM synthesis. Finally, MetK1 was introduced into yeast to redirect carbon flux toward SAM biosynthesis. As expected, the SAM production of the mutant YMig1ΔPMetK1 reached 8.91 g/L in a 10 L fermenter, which was 72.3% higher than that of the parent strain S. cerevisiae CGMCC 2842 (5.17 g/L) reported in our previous studies. This study revealed that the strategy of alleviating glucose effect and redirecting carbon flux to nonethanol products by Mig1 deletion combined with heterologous MetK1 introduction possesses great potential for improving SAM synthesis in yeast cells.