Quantum field theory is the traditional solution to the problems inherent in melding quantum mechanics with special relativity. However, it has also long been known that an alternative firstquantized formulation can be given for relativistic quantum mechanics, based on the parametrized paths of particles in spacetime. Because time is treated similarly to the three space coordinates, rather than as an evolution parameter, such a spacetime approach has proved particularly useful in the study of quantum gravity and cosmology. This paper shows how a spacetime path formalism can be considered to arise naturally from the fundamental principles of the Born probability rule, superposition, and Poincaré invariance. The resulting formalism can be seen as a foundation for a number of previous parametrized approaches in the literature, relating, in particular, "off-shell" theories to traditional on-shell quantum field theory. It reproduces the results of perturbative quantum field theory for free and interacting particles, but provides intriguing possibilities for a natural program for regularization and renormalization. Further, an important consequence of the formalism is that a clear probabilistic interpretation can be maintained throughout, with a natural reduction to non-relativistic quantum mechanics.