Tower cranes are crucial equipment for construction due to their high load-bearing capacity and efficiency in large-scale material handling. In practical applications, it is essential to ensure that payloads (end-effectors) are transported to desired positions efficiently and safely. However, tower cranes with underactuated structure often operate in complex environments and are subject to external disturbances such as payload weight and wind, such that it is difficult to guarantee the control performance. To address these issues, a nonlinear end-effector tracking controller with almost disturbance decoupling is designed for five-DOF underactuated tower cranes. First, a nonlinear coupling variable is defined based on the position of an end-effector by incorporating both actuated and unactuated states, such that the relationship between the payload position and actuated/unactuated states can be mapped directly. Besides, the almost disturbance decoupling strategy is employed to deal with uncertain external disturbances, which achieves excellent anti-swing for five-DOF tower cranes. Finally, the superiority of the developed method is verified compared with the existing almost disturbance decoupling and nonlinear block backstepping controllers through hardware experiments on an actual laboratory tower crane.