The polyphagous shot hole borer beetle (PSHB, Euwallacea fornicatus) is a pest of global significance. PSHB is an ambrosia beetle which, together with its mutualistic fungi (including Fusarium euwallaceae), can cause the death of more than 100 tree species in invaded ranges. Management of PSHB mostly relies on the removal of infested plant material. Chemical control options have been investigated only in the USA and Israel and only on a few tree species. This study evaluated four chemical treatments for the therapeutic control of PSHB on American sweetgum (Liquidambar styraciflua) in South Africa (1) bifenthrin + surfactant (alcohol ethoxylate), (2) cypermethrin + surfactant (vitamin E) + salicylic acid, (3) emamectin benzoate, and (4) propiconazole. Trees were inoculated with F. euwallaceae and mature PSHB females using a novel technique to document fungal lesion development and PSHB colony establishment success. The bifenthrin and cypermethrin treatments reduced additional PSHB colonisation attempts on treated trees by ca. 40%, while the other treatments had no effect. Colony establishment success was reduced in all treatments by between 20 and 40%. Fungal growth was inhibited only after the application of propiconazole by ca. 36%. Gallery length and the number of PSHB individuals in successful colonies were unaffected by any of the chemical treatments. These results indicate that chemical control of PSHB is only partially effective. Successful PSHB management will likely depend on a combination of chemical control options and other control strategies in an integrated pest management program.