We accomplish the complete two-loop computation of the leading-twist contribution to the photon-pion transition form factor $gamma , gamma^{ast} to pi^0$ by applying the hard-collinear factorization theorem together with modern multi-loop techniques. The resulting predictions for the form factor indicate that the two-loop perturbative correction is numerically comparable to the one-loop effect in the same kinematic domain. We also demonstrate that our results will play a key role in disentangling various models of the twist-two pion distribution amplitude thanks to the envisaged precision at Belle II.