We consider first-order differential operators with locally bounded measurable coefficients on vector bundles with measurable coefficient metrics. Under a mild set of assumptions, we demonstrate the equivalence between the essential self-adjointness of such operators to a negligible boundary property. When the operator possesses higher regularity coefficients, we show that higher powers are essentially self-adjoint if and only if this condition is satisfied. In the case that the low-regularity Riemannian metric induces a complete length space, we demonstrate essential self-adjointness of the operator and its higher powers up to the regularity of its coefficients. We also present applications to Dirac operators on Dirac bundles when the metric is non-smooth.