Benefiting from curved fibre paths, variable-angle-tow (VAT) fibre composites feature a larger design space than traditional straight-fibre reinforced plastics. Herein, an optimisation framework of a full-scale wing-box structure with VAT-fibre composites is presented, aiming at minimised mass and optimised local buckling performance under realistic aeroelastic loading conditions. Local buckling analyses on individual subsections of the wing are performed with refined finite-element models by extracting running loads from an aeroelastic analysis of the entire wing structure. Using this global–local approach, an optimisation is conducted with static failure, aeroelastic, buckling and manufacturing constraints to obtain optimised structural parameters for straight- and VAT-fibre composite wing-box architectures. By optimising wing-skin thicknesses, fibre paths and wing-spar geometry simultaneously via a genetic algorithm, the potential benefit of a VAT design is explored. In addition, the continuous tow shearing (CTS) manufacturing process, which introduces layer thickness variations as tows are steered, is explored. A mass reduction of 12.5% and 13.2% is obtained by using the constant-thickness VAT and variable-thickness CTS designs, respectively, compared to a baseline quasi-isotropic straight-fibre design. The optimised wing-skin thickness distribution also suggests that local buckling is the critical failure mode in specific regions, and therefore needs to be included during aeroelastic optimisation.