Understanding　the　roles　and　synergistic　effects　of　alloying　elements　is　crucial　for　designing　nickel-based　single　crystal　superalloys.　A　systematic　exploration　has　been　conducted　to　identify　the　synergistic　effect　of　rhenium　(Re)　and　tungsten　(W)　on　the　mechanical　properties　and　the　underlying　mechanisms　with　the　experimental　characterization　and　the　molecular　dynamics　(MD)　simulations.　The　experimental　results　show　that　the　co-addition　of　Re　and　W　not　only　has　a　significant　synergistic　strengthening　effect,　but　also　can　improve　the　work　hardening　capability.　Meanwhile,　the　co-addition　of　Re　and　W　results　in　the　majority　of　Re　and　more　W　entering　the　gamma　phase,　strengthening　the　solid　solution　and　forming　Re　segregation　and　Re-W　segregation.　That　increases　the　resistance　to　dislocation　motion　and　facilitates　the　formation　of　dislocation　tangles.　MD　simulations　reveal　that　Re　segregation　leads　to　an　extremely　inhomogeneous　distribution　of　stress　components,　which　locally　restricts　dislocation　movement.　As　a　result,　leading　dislocations　glide　via　a　series　of　forward　slip　of　local　segments,　forming　a　wavy　dislocation　line　and　reducing　the　dislocation　slip　velocity,　thereby　impeding　dislocation　motion.　These　findings　enhance　our　understanding　of　synergistic　strengthening　effects　in　the　nickel-based　single　crystal　superalloys.