By brush seal, we mean a type of mechanical seal that uses a large number of closely packed, thin, and flexible bristles to create an outstanding seal between rotating and stationary components in gas turbine engines. However, at high levels of swirling and pressured environments in engines, bristles of brush seals tend to circumferentially slip, which leads to reduced sealing performance and seal failure. In this paper, the effects of upstream–downstream pressure differences Δp (0.2–0.5 MPa), downstream static pressure (0.1–1.0 MPa), and the coverage of bristles by a front plate (0%–90%) on the mechanical characteristics and deflections of bristles of a brush seal at highly swirling inlet were investigated based on a two-way fluid-structure coupling method. A key criterion for bristle instability, based on a simplified two-dimensional (2D) theoretical analysis, is obtained from the fluid-structure coupling simulations. The results indicate that a fundamental reason for the bristle circumferential slip is the ratio of the normal to the axial aerodynamic forces (Fn/Fax) acting on the first row of bristles. When this ratio exceeds 0.9, the bristles will slip circumferentially. The effects of the pressure differential across the seal, the downstream pressure, inlet swirl velocity, and front plate coverage of the bristles on bristle stability can all be explained through their influences on this force ratio. At relatively low outlet static pressure of 0.1 MPa, upstream bristles slip when the inlet swirl is in the range of 230–300 m/s and the bristle slip instability is more likely to occur at higher pressure difference conditions. However, at high downstream pressures, Fn/Fax declines with the growth of Δp, contributing to the stability tendency. With the constant Δp, the value of Fn/Fax significantly increases as the downstream pressure rises, and the critical swirl velocity required to trigger bristle slip is considerably reduced. Additionally, the front plate shields a part of the bristles away from pressure gradient in axial direction but leads to outward radial flow upstream of the bristle pack, thereby increasing the Fn/Fax. Thus, front plate does not offer protection to bristles under high inlet swirl conditions, on the contrary, it may cause early slip of the bristles.