Ligand binding sites in proteins are often localized to deeply buried cavities, inaccessible to bulk solvent.Yet, in many cases binding of cognate ligands occurs rapidly. An intriguing system is presented by the L99A cavity mutant of T4 Lysozyme (L99A T4L) that rapidly binds benzene (~10 6 M -1 s -1 ). Although the protein has long served as a model system for protein thermodynamics and crystal structures of both free and benzene-bound L99A T4L are available, the kinetic pathways by which benzene reaches its solventinaccessible binding cavity remain elusive. The current work, using extensive molecular dynamics simulation, achieves this by capturing the complete process of spontaneous recognition of benzene by L99A T4L at atomistic resolution. A series of multi-microsecond unbiased molecular dynamics simulation trajectories unequivocally reveal how benzene, starting in bulk solvent, diffuses to the protein and spontaneously reaches the solvent inaccessible cavity of L99A T4L. The simulated and high-resolution Xray derived bound structures are in excellent agreement. A robust four-state Markov model, developed using cumulative 60 µs trajectories, identifies and quantifies multiple ligand binding pathways with low activation barriers. Interestingly, none of these identified binding pathways required large conformational changes for ligand access to the buried cavity. Rather, these involve transient but crucial opening of a channel to the cavity via subtle displacements in the positions of key helices (helix4/helix6, helix7/helix9) leading to rapid binding. Free energy simulations further elucidate that these channel-opening events would have been unfavorable in otherwise ligand-inactive wild type T4L. Taken together, by integrating experiments, these simulations provide unprecedented mechanistic insights into complete ligand recognition process in a buried cavity. By illustrating the power of subtle helix movements in opening up multiple pathways for ligand access, this work offers an alternate view of ligand recognition mechanism in a solvent-inaccessible cavity, contrary to common perception of single dominant pathway for ligand binding.