The influence of surface roughness in a rail/wheel contact has been a concern for railway owners since the introduction of ‘rail grinding' as a maintenance strategy. Presently, there are no well-defined guidelines regarding the surface topographies of ground rails and re-turned wheels. There is thus a need to establish scientific guidelines regarding the surface topographies for the rails and wheels in order to minimize grinding costs/time and to improve rail/wheel performance. This study is aimed at investigating the influence of surface topographies of wheels and rails on running-in behaviour, wear, friction, and the resultant surface damage through experimental simulation in the laboratory. A two-disc rolling/sliding test machine has been used in this experimental work. Two different roughness values were produced on both the rail and wheel test specimens. A design of experiment approach has been used to conduct experiments and to analyse the results. The results show that the surface roughness values of the specimens in some material pairs do influence wear, friction, and resulting surface damage.