The practical output containment problem for heterogeneous nonlinear multiagent systems under external disturbances generated by an exosystem is investigated in this article. It is required that the outputs of followers converge to the predefined convex combination of leaders' outputs. One of the major challenges in solving such a problem lies in dealing with the coupling among different nonlinearities, state dimensions, and system matrices of heterogeneous agents. To overcome the aforementioned challenge, a distributed observer-based control protocol is developed and employed. First, an adaptive state observer for estimating the states of all the leaders is constructed based on the neighboring interactions. Second, two new classes of observers are constructed for each follower exploiting the output information of the follower, in which the adaptive neural networks (NNs)-based approximation is exploited to compensate for the unknown nonlinearity in the followers' dynamics. A practical output containment control protocol is then generated by the proposed observers, where the control parameters are determined by an algorithm including two steps. Furthermore, with the help of the Lyapunov stability theory and the output regulation method, the practical output containment criteria for the considered closed-loop system under the influences of external disturbances are derived on the basis of the presented control protocol. Finally, the derived theoretical results are illustrated by a simulation example.