The invention belongs to a mixed-voltage high-frequency multi-layer circuit board, a fabrication method thereof and a high-frequency electronic component, which are used for solving the problem of unreasonable design of the prior art. The fabrication method of the mixed-voltage high-frequency multi-layer circuit board comprises the following steps of A, material preparation; B, lamination; and C, copper plating. The mixed-voltage high-frequency multi-layer circuit board comprises a circuit board body, wherein a plurality of penetrating through holes are formed in the circuit board body and pass through the thickness direction of the circuit board body, a copper plating layer is arranged on the hole wall of each penetrating through hole, the circuit board body comprise two layers of polytetrafluoroethylene fiberglass fabric copper cladding foil plates, a plurality of polyimide thin film copper cladding layers are arranged between the two layers of polytetrafluoroethylene fiberglass fabric copper cladding foil plates and are sequentially laminated, and a circuit layer is arranged on at least one surface of each polyimide thin film copper cladding layer. The mixed-voltage high-frequency multi-layer circuit board has the advantages that the high-frequency dielectric property and the high-temperature resistant performance can be improved, and the inter-layer alignment accuracy can be improved.