Nanocarrier (NC)‐mediated drug delivery is widely researched in medicine but to date has not been used in agriculture. The first curative NC‐based treatment of the worldwide occurring grapevine trunk disease Esca, with more than 2 billion infected plants causing a loss yearly of $1.5 billion, is presented. To date, only repetitive spraying of fungicides is used to reduce chances of infection. This long‐term treatment against Esca uses minimal amounts of fungicide encapsulated in biobased and biodegradable lignin NCs. A single trunk injection of <10 mg fungicide results in curing of an infected plant. Only upon Esca infection, ligninolytic enzymes, secreted by the Esca‐associated fungi, degrade the lignin NC to release the fungicide. The specific antifungal activity is confirmed in vitro and in planta (in Vitis vinifera L. cv. ‘Portugieser’). All treated plants prove to exhibit significantly fewer symptoms several weeks after treatment, and their condition is monitored for 5 years (2014–2018), proving a long‐term curative effect of this NC treatment. This study proves the efficacy of this NC‐mediated drug delivery for agriculture, using a minimum amount of fungicides. It is believed that this concept can be extended to other plant diseases worldwide to reduce extensive spraying of agrochemicals.