The invention relates to a synthesis method of semaglutide. According to the method, a semaglutide product is synthesized by adopting a solid-liquid phase combination method, and three fragments are simultaneously synthesized in a synthesis manner of 16+6+9 fragments, and therefore, the synthesis time of the product is greatly shortened; moreover, by step-by-step analysis on synthesis factors of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly, Gln-Ala-Ala-N6-[N-(17-carboxy-1-oxoheptadecyl-L-gama-glutamyl [2-(2-aminoethoxy) ethoxy] acetyl [2-(2-aminoethoxy) ethoxy] acetyl]-Lys-Glu-Phe, Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH and the like, the difficulty in synthesis of a peptide sequence in solid-phase synthesis is reduced, the problem of batch amplification in the solid-phase synthesis is solved, and the synthesis efficiency is improved; and as liquid-phase fragment synthesis is adopted, the purification difficulty is effectively reduced, and the production cost is greatly lowered. The synthesis method disclosed by the invention has the advantages that the synthesis time can be shortened by 40%, the cost of materials is lowered, the generation quantities of deletion peptide and hybrid peptide are decreased, and the synthesis method is suitable for industrial large-scale production.