This paper investigates the event-triggered leader-following consensus problem for a multi-agent system with semi-Markov switching topologies. A sampled-data-based event-triggered transmission scheme is introduced to reduce unnecessary communication. By modeling the switching of network topologies by a semi-Markov process and adopting an event-triggered transmission scheme, a new consensus protocol is proposed. Compared with the traditional Markovian switching topologies, the transition rates in the semi-Markov switching topologies are time-varying, which is more general and practicable. Through utilization of an appropriate Lyapunov–Krasovskii functional, some sufficient conditions are derived, which guarantee that the leader-following consensus can be achieved in mean-square sense. Moreover, the consensus gain matrices and parameter of the event-triggered scheme can be efficiently solved out. Finally, a numerical example illustrates the effectiveness of the proposed design technique.