We describe a quantum limit to measurement of classical spacetimes. Specifically, we formulate a quantum Cramer-Rao lower bound for estimating the single parameter in any one-parameter family of spacetime metrics. We employ the locally covariant formulation of quantum field theory in curved spacetime, which allows for a manifestly background-independent derivation. The result is an uncertainty relation that applies to all globally hyperbolic spacetimes. Among other examples, we apply our method to detection of gravitational waves using the electromagnetic field as a probe, as in laser-interferometric gravitational-wave detectors. Other applications are discussed, from terrestrial gravimetry to cosmology.