Most respiratory infectious disease transmission events occur in indoor environments, and examining the infection risk in different types of multi-zone buildings is critical to the safe reopening and use of public buildings. Appropriate space design influences occupant behavior and virus spread, thereby aiding in mitigating indoor infection risk. This study aims to quickly evaluate the multi-route infection risk in multi-zone buildings with relatively stable occupant populations, and to quantify the effectiveness of spatial interventions at different levels. A Markov chain-based approach was proposed to characterize occupants' time-activity trajectories with low time cost and relatively high accuracy. Four transmission routes are considered, especially for the fine-grained characterization of close contact. A real university office building was selected as a case study to quantitatively evaluate the effects of three non-pharmacological interventions including spatial layout, ventilation, and occupant behavioral control. Results showed that short-range airborne transmission dominated, and optimized combination spatial design interventions reduced the indoor infection risk by up to 10 %. Zone layout intervention was the most effective, with the division of the open-plan office area into three subzones, reducing the risk by 9.6 %, which was superior to the intervention of maintaining a one-meter interpersonal distance. Followed by the furniture layout, without changing the seating capacity and without desktop baffles, the L-shaped table layout worked better reducing the risk by 2.78 %. This study can help architects and managers better understand the risk of indoor transmission in multizone buildings from a spatial design perspective, to select appropriate interventions to reduce the risk.