• Two 2-(2-phenethyl)chromone derivatives were isolated from agarwood of Aquilaria walla . • Compound 1 is a new dimeric 2-(2-phenethyl)chromone. • Compound 2 is a unprecedented flavonoid-2-(2-phenethyl)chromone. • Compounds 1 and 2 showed cytotoxic activity against five human cancer cell lines. Two new 2-(2-phenethyl)chromone derivatives were isolated from agarwood of Aquilaria walla , including a dimeric 2-(2-phenethyl)chromone ( 1 ) and a flavonoid-2-(2-phenethyl)chromone ( 2 ). Their structures were established based on spectroscopic methods including HRESIMS, 1D, and 2D NMR. Compounds 1 and 2 showed cytotoxic activity against five human cancer cell lines with IC 50 values ranging from 4.96–44.34 μ M.