Herein, a ruthenium-mediated remote C-H mono- and disulfonylation of 2-pyridones with arylsulfonyl chlorides is developed. The catalytic system consisting of a [Ru(p-cymene)Cl2]2 catalyst and KOAc additive allows 2-pyridones to undergo C3,C5-disulfonylation in 1,4-dioxane, and C5-sulfonylation when the C3-position of 2-pyridones is blocked. The successful transformation of the products and late-stage modification of estrone further highlighted the potential utility and significance of this synthetic protocol. Preliminary mechanistic studies indicated that the remote regioselectivity might be dictated via chelation-assisted ruthenation.