This article presents a comparative study of the effect of steel layouts on the seismic behavior of transition steel-concrete composite connections, both experimental and analytical investigations of concrete filled steel tube-reinforced concrete (CFST-RC) and steel reinforecd concrete-reinforced concrete (SRC-RC) structures were conducted. The steel-concrete composite connections were subjected to combined constant axial load and lateral cyclic displacements. Tests were carried out on four full-scale connections extracted from a real project engineering with different levels of axial force. The effect of steel layouts on the mechanical behavior of the transition connections was evaluated by failure modes, hysteretic behavior, backbone curves, displacement ductility, energy dissipation capacity and stiffness degradation. Test results showed that different steel layouts led to significantly different failure modes. For CFST-RC transition specimens, the circular cracks of the concrete at the RC column base was followed by steel yielding at the bottom of the CFST column. While uncoordinated deformation could be observed between SRC and RC columns in SRC-RC transition specimens, the crushing and peeling damage of unconfined concrete at the SRC column base was more serious. The existences of I-shape steel and steel tube avoided the pinching phenomenon on the hysteresis curve, which was different from the hysteresis curve of the general reinforced concrete column. The hysteresis loops were spindle-shaped, indicating excellent seismic performance for these transition composite connections. The average values of equivalent viscous damping coefficients of the four specimens are 0.123, 0.186 and 0.304 corresponding to the yielding point, peak point and ultimate point, respectively. Those values demonstrate that the transition steel-concrete composite connections have great energy dissipating capacity. Based on the experimental research, a high-fidelity ABAQUS model was established to further study the influence of concrete strength, steel grade and longitudinal reinforcement ratio on the mechanical behavior of transition composite connections.