Based on the pharmaceutical importance of the coumarin scaffold, we decided here to synthesize and evaluate the biological activity of some new coumarins. The new coumarin derivatives were synthesized starting from 3-(2-bromoacetyl)-2H-chromen-2-one (1) and their structures were clarified by fully spectral data. Ten of the new synthesized compounds were investigated for their anticancer activity against 60 human cancer cell lines by NCI USA. All the tested compounds showed good to mild activity against the tested cancer cell lines. Compounds 5, 7, and 8 were the most active against Renal Cancer UO-31 cancer cell line with growth inhibition percentage of 38.74%, 45.09%, and 34.65%, respectively. Where, compound 12 demonstrated strong to moderate activity toward Leukemia K-562, Renal Cancer UO-31and Breast Cancer T-47D cancer cell lines with growth inhibition percentage of 27.00%, 31.59%, and 32.98%, respectively.