The first paper of this series introduced objects (elements of twisted relative cohomology) that are Poincaré dual to Feynman integrals. We show how to use the pairing between these spaces — an algebraic invariant called the intersection number — to express a scattering amplitude over a minimal basis of integrals, bypassing the generation of integration-by-parts identities. The initial information is the integrand on cuts of various topologies, computable as products of on-shell trees, providing a systematic approach to generalized unitarity. We give two algorithms for computing the multi-variate intersection number. As a first example, we compute 4- and 5-point gluon amplitudes in generic space-time dimension. We also examine the 4-dimensional limit of our formalism and provide prescriptions for extracting rational terms.