We study the question whether rational homogeneous spaces are rigid under Fano deformation. In other words, given any smooth connected family \(\pi :{{\mathcal {X}}}\rightarrow {{\mathcal {Z}}}\) of Fano manifolds, if one fiber is biholomorphic to a rational homogeneous space S, is \(\pi \) an S-fibration? The cases of Picard number one were answered by Hwang and Mok. The manifold \({{\mathbb {F}}}(1, Q^5)\) is the unique rational homogeneous space of Picard number one that is not rigid under Fano deformation, and a Fano degeneration of it is constructed by Pasquier and Perrin. For higher Picard number cases, one notices that the Picard number of a rational homogeneous space G/P satisfies \(\rho (G/P)\le \mathrm{rank}(G)\). Weber and Wiśniewski proved that the rational homogeneous spaces G/P with \(\rho (G/P)=\mathrm{rank}(G)\) (i.e. complete flag manifolds) are rigid under Fano deformation. In this paper, we show that the rational homogeneous spaces G/P with \(\rho (G/P)=\mathrm{rank}(G)-1\) are rigid under Fano deformation, provided that G is a simple algebraic group of type ADE, and G/P is not biholomorphic to \({{\mathbb {F}}}(1, 2, {{\mathbb {P}}}^3)\) or \({{\mathbb {F}}}(1, 2, Q^6)\). We also show that \({{\mathbb {F}}}(1, 2, {{\mathbb {P}}}^3)\) has a unique Fano degeneration, which is explicitly constructed. Furthermore, the structure of possible Fano degenerations of \({{\mathbb {F}}}(1, 2, Q^6)\) is also described explicitly. Our main result is obtained by applying the theory of Cartan connections and symbol algebras.