In view of the multifunctional features of coumarins and chalcones, coumarin-chalcone hybrids have attracted much attention in recent years. Herein, the free radical scavenging activities of a series of coumarin-chalcone hybrids were investigated using the density functional theory (DFT) method. Three main reaction mechanisms were explored: hydrogen atom transfer (HAT), electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET). Thermodynamic descriptors associated with these mechanisms were calculated in the gas phase and solvents. The results demonstrate that the predicted antioxidant efficiencies are generally in accordance with the experimental results. HAT is proposed as the thermodynamically favored mechanism in the gas phase and nonpolar solution, while SPLET is preferred in polar media. Our results indicate that compound MPHCC possesses potential for inactivating free radicals via double HAT and double SPLET mechanisms depending upon the polarity of environment. In addition, the SPLHAT mechanism provides an alternative pathway to HAT and SPLET for radical scavenging by MPHCC and OPHCC. The results confirmed the crucial role of hydroxyl groups on the chalcone moiety in trapping radicals. 4'-OH in the catechol group is proposed as the primary target for radical attack.