A series of coumarin‐substituted 1,3‐thiazin‐2‐thione derivatives 4a–m were synthesized via the multicomponent reaction of 3‐chloro‐3‐(2‐oxo‐2H‐chromen‐3‐yl)acrylaldehyde (1) carbon disulfide (2), and various primary amines (3), in presence of triethylamine and acetonitrile under stirring with good yields. Compounds 4a, 4d, and 4m showed activity against A549, MDA‐MB‐231, MCF7, HeLa, and B16F10 cancer cell lines. In vitro anticancer result was supported by in silico docking and in silico ADME as well.