Artemisia selengnesis Turcz (AST) is a commonly consumed medicinal and culinary herb in China. This study aimed to obtain the proper solvent for extracting bioactive compounds from AST guided by antioxidant activity, and characterize the major chemical components by HPLC-QTOF-MS/MS. The results showed that 50% ethanol extract of AST (FEE) exhibited the highest total phenolics (17.03 mg GAE/g DM) and total flavonoids content (11.11 mg RT/g DM), while water extract (WE) contained the richest polysaccharide (102.43 mg Glu/g DM). The best DPPH scavenging capacity (IC50 = 0.74 mg DM/mL) and reducing power (IC0.5 = 2.18 mg DM/mL) were observed in FEE followed by WE. Correlation analysis revealed that phenolics showed the highest correlation with DPPH scavenging ability (r = 0.930) and reducing power (r = 0.975). Ethanol at 50% can be an efficient solvent for extracting antioxidants from AST based on the study. Total 27 compounds including 11 organic acids (7 hydroxycinnamic acids), 1 amino acid and 15 fatty acids were identified or tentatively identified from FEE. Notably, unsaturated fatty acids with 18 carbons were identified in Artemisia genus for the first time. Quinic acid, 3-, 5-caffeoylquinic acid and 3,4-, 3,5-dicaffeoylquinic acid were identified as the major phenolic acids in AST extract, and they were identified in AST for the first time.