The invention relates to a multi-ball setting shaft stop valve, which comprises a valve body and a valve seat, wherein the valve seat is positioned in a cavity of the valve body, and is pushed by a fluid to slide and set in the valve body, and the valve body is formed by detachably connecting an upper joint with a lower joint; a connecting part of the upper joint and the lower joint is sealed, and the valve seat is a piston; the piston is provided with at least two penetrating flow channels, and a transition part for guiding a plurality of balls to move to each setting position is arranged at a flow channel inlet. When the post-set balls move to the flow channel inlet, the set balls and the transition part form a guide channel for the post-set balls to move to the setting positions. The stop valve has enough large flow capacity to ensure the smooth slurry replacement and ball injection operations, and avoids the advanced setting caused by the cut-off function of the flow channel; the structural design is simple and reasonable, the stop valve is not only more suitable for processing and manufacturing, but also additional tooling is not needed in the assembly, disassembly and maintenance process; the operation is simple.