A strong wind would cause roof openings on a low-rise building and bring further structural damage. Previous related studies focused on different shapes of openings on flat roofs. Little study has been done on the sloped roofs with openings in vulnerable roof areas. In this study, wind tunnel tests were carried out to investigate the steady-state and transient internal pressure characteristics due to opening at the vulnerable roof areas of a low-rise building. The tests considered both steady-state and transient openings of roof. The experimental results indicated that the steady-state internal pressure distribution tends to be uniform and that the internal pressure induced by leeward roof ridge opening is obviously lower than that induced by the windward one. The fluctuation effect around the orifice area is apparent with the skewed wind direction and the combined effect of internal and external pressures on the unopened roof side is significantly smaller than that on the opened side. Current design provision of China for internal pressure evaluation is found to be unconservative. The transient overshoot is closely related to the opening location in the vulnerable roof area and is more pronounced when the opening is on the leeward side. Among the internal pressure coefficients commonly adopted in design, the extreme net wind pressure coefficient is most important, which is affected most at the orifice near eaves, roof corners and tails, and leeward roof ridge.