Gradient-structured　CoCrFeMnNi　high-entropy　alloy　(HEA)　with　all　grain　sizes　lying　in　the　inverse　Hall-Petch　range　exhibits　a　significant　synergistic　softening　behavior,　with　the　yield　strength　even　lower　than　the　rule　of　mixtures　(ROM)　under　uniaxial　tensile　loading.　The　softening　of　grain　boundaries　(GB)　is　very　pronounced　in　hard　domains　due　to　the　extremely　small　grain　size.　Moreover,　the　coordinated　deformation　of　heterostructure　promotes　grain　rotation　in　soft　domains　with　large　grain　sizes.　However,　the　extra　strength　generated　by　hetero-deformation　induced　(HDI)　strengthening　increases　with　increasing　volume　fraction　of　hard　domain,　contributing　to　a　gradual　decrease　in　the　gap　between　yield　strength　and　ROM.　Here,　we　identify　multiple　deformation　mechanisms　promoted　by　mechanical　incompatibility　through　molecular　dynamics　(MD)　simulations.　On　the　one　hand,　the　higher　volume　fraction　of　the　hard　domain　encourages　the　adaptation　of　dislocation-mediated　activities　to　plastic　strains,　thus　reducing　the　possibility　of　GB　sliding　or　intergranular　brittle　cracking.　More　importantly,　soft　domains　are　more　susceptible　to　detwinning　under　additional　compressive　stress,　which　induces　grain　refinement　in　localized　regions　and　contributes　extra　strength.　Observation　of　the　strain　distribution　reveals　that　the　banded　shear　bands　(SBs)　are　spread　throughout　the　soft　domains,　which　effectively　improves　strain　gradient　strengthening.　It　has　been　verified　that　the　gradient　structure　has　the　highest　extra　strength　at　the　hard　domain　volume　fraction　of　40–50%.　The　findings　provide　insights　into　the　engineering　applications　of　gradient-structured　HEA.　©　2024　Elsevier　Ltd