Uneven pressure drops among stages of multistage brush seal (MBS) leads to early failure of single-stage seal units, which directly affects service life of the seal used in aeroengines, gas turbines, and steam turbines. In this paper, influence factors of interstage pressure drop were studied to analyze formation mechanism of the uneven pressure drops. Moreover, an MBS with differentiated structure was presented, and its interstage pressure drops were further investigated. The results showed that the MBS with several same single-stage seal units had uneven pressure drops among stages under high inlet/outlet pressure ratios. In view of remarkably increasing velocity and decreasing pressure in downstream region of bristle pack near rotor surface during flow of airflow, adjustments of structural parameters (i.e., increasing height of backing plate to rotor surface Hb, increasing seal clearance Hg, and decreasing axial width of bristle pack B) could improve the uneven pressure drops among different stages due to increasing outlet air flow area of the stage. The closer pressure drop proportions of different stages to ideal average value indicated increase of Hb had a more effective effect to balance the pressure drops among different stages compared to increase of Hg and decrease of B. An MBS with differentiated structure, in which both Hb and Hg of all the single-stage seal units were increased progressively and B was decreased step by step, showed a good performance to obtain even interstage pressure drops.