Using a sample of (2.712 ± 0.014) × 109 ψ(3686) events collected with the BESIII detector at the electron positron collider BEPCII, the decay ψ(3686) → $ {\Xi}^{-}{K}S^0{\overline{\varOmega}}^{+} $ + c.c. is observed for the first time, which has a significance of 5.9 standard deviations. The branching fraction of this decay is measured to be (2.91 ± 0.47 ± 0.33) × 10 −6, where the first and second uncertainties are statistical and systematic, respectively. The ratio between $ {\mathcal{B}}{\psi (3686)\to {\varXi}^{-}{K}S^0{\overline{\varOmega}}^{+}+c.c} $ and $ {\mathcal{B}}{\psi (3686)\to {\varOmega}^{-}{K}^{+}{\overline{\Xi}}^0+c.c} $ is determined to be 1.05 ± 0.23 ± 0.14, which deviates from the isospin symmetry conservation predicted value of 0.5 by 2.1σ.