Improved beam-to-column joint configurations, with the beam plastic hinges shifted away from the column faces, were required in high strength steel frames to guarantee the seismic performance, and the flange-plate beam-to-column joints are expected to be one of the improved joint configurations that have good prospects in high strength steel frames because of the potential reinforcing effects and the negligible additional requirements for construction space. However, there have been few investigations on the high strength steel flange-plate beam-to-column joints and a lack of detailed design method for flange-plate joints. Considering three different combinations of Q345 or Q460 steel beams and Q460 or Q890 steel columns, a total of 6 full-scale specimens of flange-plate beam-to-column joints with middle columns in steel frames were designed and tested subjected to anti-symmetrical cyclic loads. The failure modes, the resistance, the stiffness and the ductility of the specimens were analysed, and the influences of the joint configurational parameters, including the panel zone thickness, the flange-plate lengths, the attached fillet welds in web connections and the fillet welds arrangements around the flange plates, were investigated. According to the test results, continuity plates with enough thickness were necessary in high strength steel flange-plate joints to avoid unexpected failure modes, and the panel zone shear rotation would make a considerable contribution to the total story drift angles and the plastic story drift angles of the high strength steel frames. Five of the tested specimens reached a story drift angle larger than 0.035 rad and one of them was larger than 0.04 rad, indicating that the flange-plate joint configurations could develop a considerable ductility, which, however, may still be insufficient when adopted in structures with high ductility demand. Based on the test results, design recommendations were proposed for flange-plate beam-to-column joints in high strength steel frames.