Fresh-sliced button mushrooms (Agaricus bisporus) are extremely perishable and deteriorate much faster than intact fruit bodies during storage. The aim of this study was to investigate the effects of different concentrations of arginine on the storage quality of fresh-sliced A. bisporus. All the arginine treatments showed the ability to maintain the quality of fresh-cut A. bisporus. The 0.4 mM arginine treatment most effectively maintained the sensory properties of fresh-cut button mushrooms because it delayed browning and weight loss, inhibited the increase in malondialdehyde content and polyphenol oxidase (PPO) activity, and promoted the activity of peroxidase and catalase, and increased the content of total phenolic and flavonoid substances. The 0.4 mM arginine treatment also significantly lowered the expression levels of three PPO genes on day 2. These results indicate that arginine treatment has a great potential to be applied for the quality retention of fresh-sliced mushrooms during storage. Practical applications This research reveals the ability of arginine as a preservative to prolong the storage life of mushroom slices. The completion of this research also provides a new and helpful insight into the preservation approach of fresh-cut products.