The invention provides a manufacturing method of waterproof and breathable leather. The method comprises the following steps: predetermined cow wet blue leather is selected as crust, and the crust is then sequentially subjected to the procedures of acid rewetting, retanning, neutralization, filling, dyeing and fat liquoring; a waterproof agent adopted in the fat liquoring procedure is a polymer dispersant containing silicon resin. The method provided by the invention has the advantages that the polymer dispersant containing the silicon resin is used as the waterproof agent and replaces a fluoride waterproof agent adopted in the traditional method, so that hydrophobic layers with the waterproof and breathable effects can be formed on the leather surface and in the leather, and the obtained leather further achieves waterproof performance and breathable performance as well as lower cost.