Joint prevention and control of transboundary pollution in multi-regional basins has been the focus of the international community. This paper explores a joint decision problem of transboundary water pollution involving three regions based on differential game theory. The pollution control strategies assumed by three differential game models, independent, two-party joint and three-party cooperation, and the emission trading system is taken into consideration. We found that strengthening inter regional alliance cooperation in the basin is conducive to reducing pollution emissions and releasing more investment potential for pollution control, so as to optimize the decision-making purpose of transboundary pollution prevention and control. For the reduction strategy of pollution stock, the correlation between participants is more important than the strength of the alliance, and the strategy selection of downstream areas plays an important role in the effect of joint prevention and control of pollution in river basins. Policy suggestions on joint multi-regional transboundary pollution control based on different target time periods are put forward.