Polypropylene (PP) fibers are usually applied to alleviate or prevent the explosive spalling of high-performance concrete (HPC) when exposed to fire. This paper presents an extensive experimental study on the fire response of frame structures constructed with HPC as well as the post-fire seismic performance. In total, four single-span and single-story frames were designed and cast with HPC blast-furnace slag (HPC-BFS). Three of them which were subjected to constant vertical loads were tested under the ISO-834 fire. These three fire-exposed frames together with one fire-unexposed frame then underwent low-frequency cyclic loading. Based on the fire test results, fire responses including temperature field and frame deformations during both heating and cooling stages are investigated. This is followed by a discussion of seismic behavior of these fire-exposed frames, where effects of concrete strength and PP fibers on the fire resistance as well as the post-fire seismic behavior are examined.