Motivated by the vital role played by grain boundaries and interfaces in Ni-based superalloys in influencing mechanical properties such as creep rupture strength, fatigue crack growth rates and resistance towards environmental embrittlement, we use first-principles simulations to estimate fracture strengths of Ni Σ3(111) grain boundary, Ni Σ5(012) grain boundary, Ni/Ni 3 Al interfaces and Ni/boride interfaces through determination of their work of separation. We find that Ni/boride interfaces have higher fracture strengths than the other commonly occurring interfaces in Ni-alloys, such as NiΣ5 & NiΣ3 grain boundaries and coherent Ni/Ni 3 Al interfaces, and are less susceptible to oxygen-induced embrittlement. Our calculations show how the presence of Mo at Ni/M 5 B 3 (M = Cr, Mo) interfaces leads to additional reduction in oxygen-induced embrittlement. Through Electron-LocalizationFunction based analyses, we identify the electronic origins of effects of alloying elements on fracture strengths of these interfaces and observe that chemical interactions stemming from electronegativity differences between different atomic species are responsible for the trends in calculated strengths. Our findings should be useful towards designing Ni-based alloys with higher interfacial strengths and reduced oxygen-induced embrittlement.