We develop the connection between large deviation theory and more applied approaches to stochastic hybrid systems by highlighting a common underlying Hamiltonian structure. A stochastic hybrid system involves the coupling between a piecewise deterministic dynamical system in $R^d$ and a time-homogeneous Markov chain on some discrete space $\Gamma$. We assume that the Markov chain on $\Gamma$ is ergodic, and that the discrete dynamics is much faster than the piecewise deterministic dynamics (separation of time-scales). Using the Perron-Frobenius theorem and the calculus-of-variations, we evaluate the rate function of a large deviation principle in terms of a classical action, whose Hamiltonian is given by the Perron eigenvalue of a $|\Gamma|$-dimensional linear equation. The corresponding linear operator depends on the transition rates of the Markov chain and the nonlinear functions of the piecewise deterministic system. The resulting Hamiltonian is identical to one derived using path-integrals and WKB methods. We illustrate the theory by considering the example of stochastic ion channels.