Pedestrian priority is an important requirement for city centre regeneration. The quantitative analysis of the separation degree of pedestrians and vehicles is a key technique to measure the walkability of city centre regeneration. This paper proposes a method for measuring the walkability of the spatial structure in city centres, based on spatial topological relationships. Using space syntax as a platform, the walkability of the spatial structure of city centres is quantitatively analysed from the perspective of separation of pedestrians and vehicles, and the regeneration of pedestrianisation. Based on 21 cases of major city centres in the United Kingdom (UK), the trend of pedestrianisation regeneration from the early 20th century to the present is analysed. The analysis of the separation degree of pedestrians and vehicles and the analysis of regeneration models and the comparative analysis found that: (1) from the early 20th century to the present, the spatial structure of major city centres in the UK clearly trended toward pedestrianisation. (2) The regeneration process can be categorised into three models: the Gradual Growth Model, One Step Model and Long-Term Planning Model. (3) The three models contribute differently to the separation of pedestrians and vehicles in city centres, and their advantages and disadvantages differ. This study has implications for the theory and practice of pedestrianisation regeneration in city centres.