Significance Cells need to rapidly control their cell cycle profile, gene expression, or protein stability in response to the activation of stress-response pathways. One such type of stress results from plasma membrane damage, which can arise because of physical damage or pathogen invasion. Here, we report that plasma membrane stress inhibits polarized cell growth and DNA replication through a novel cell cycle checkpoint pathway in Saccharomyces cerevisiae . To our knowledge, this is the first study to link a plasma membrane signaling pathway with the cell cycle and DNA replication control, which is relevant to plasma membrane repair and the role of stress and cell proliferation control in higher eukaryotes.