The global well-posedness of the Boltzmann equation with initial data of large amplitude has remained a long-standing open problem. In this paper, by developing a new L x L v 1 L x , v approach, we prove the global existence and uniqueness of mild solutions to the Boltzmann equation in the whole space or torus for a class of initial data with bounded velocity-weighted L x L v 1 L x , v norm under some smallness condition on the L x L v 1 L x , v norm as well as defect mass, energy and entropy so that the initial data allow large amplitude oscillations. Both the hard and soft potentials with angular cut-off are considered, and the large time behavior of solutions in the L x L v 1 L x , v norm with explicit rates of convergence are also studied.