Longitudinal ventilation is widely employed for smoke control in tunnels due to its relatively low installation cost and compactness. However, smoke control using a longitudinal ventilation system becomes complex when applied in a multi-branch sloping tunnel. In sloping tunnels, the stack effect and forced longitudinal ventilation may combine to produce multiple smoke flow patterns, even under identical or similar boundary conditions. Furthermore, such flow multiplicity behavior is considerably more complicated in a multi-branch sloping tunnel than in a single sloping tunnel. In this paper, an optimal longitudinal ventilation strategy was proposed to prevent smoke flow multiplicity induced by the combined buoyancy- and pressure-driven effects of a downhill sloping, longitudinally ventilated multi-branch tunnel fire. The ventilation network of the multi-branch tunnel was divided into three basic regions: the branches upstream of the intersection node, an on/off-ramp, and the other branches downstream of the intersection node. Based on this division and a hydraulic analysis, the multi-branch tunnel was characterized as a system consisting of several three-branch structures. The critical fan-induced pressure rise required to prevent smoke flow multiplicity was then derived by a potential analysis method according to the fire location in the tunnel. The optimal strategy was achieved by integrating the fan-induced pressure rises in each tunnel branch. The results reveal that the total pressure at the branch intersection node can be varied to regulate the integrated fan-induced pressure rise in each branch. The efficiency of this strategy in preventing flow multiplicity for all typical fire source locations in a three-branch structure was then demonstrated via numerical simulations. The proposed approach has implications for improving tunnel emergency ventilation design and fire protection.