We study Lord Rayleigh's problem for clamped plates on an arbitrary n-dimensional (n ≥ 2) Cartan-Hadamard manifold (M, g) with sectional curvature K ≤ −κ 2 for some κ ≥ 0. We first prove a McKean-type spectral gap estimate, i.e. the fundamental tone of any domain in (M, g) is universally bounded from below by (n−1) 4 16 κ 4 whenever the κ-Cartan-Hadamard conjecture holds on (M, g), e.g. in 2-and 3-dimensions due to Bol (1941) and Kleiner (1992), respectively. In 2-and 3-dimensions we prove sharp isoperimetric inequalities for sufficiently small clamped plates, i.e. the fundamental tone of any domain in (M, g) of volume v > 0 is not less than the corresponding fundamental tone of a geodesic ball of the same volume v in the space of constant curvature −κ 2 provided that v ≤ cn/κ n with c2 ≈ 21.031 and c3 ≈ 1.721, respectively. In particular, Rayleigh's problem in Euclidean spaces resolved by Nadirashvili (1992) and Ashbaugh and Benguria (1995) appears as a limiting case in our setting (i.e. K ≡ κ = 0). Sharp asymptotic estimates of the fundamental tone of small and large geodesic balls of low-dimensional hyperbolic spaces are also given. The sharpness of our results requires the validity of the κ-Cartan-Hadamard conjecture (i.e. sharp isoperimetric inequality on (M, g)) and peculiar properties of the Gaussian hypergeometric function, both valid only in dimensions 2 and 3; nevertheless, some nonoptimal estimates of the fundamental tone of arbitrary clamped plates are also provided in high-dimensions. As an application, by using the sharp isoperimetric inequality for small clamped hyperbolic discs, we give necessarily and sufficient conditions for the existence of a nontrivial solution to an elliptic PDE involving the biharmonic Laplace-Beltrami operator.2000 Mathematics Subject Classification. Primary: 35P15, 53C21, 35J35, 35J40.