Research on factors affecting rolling contact fatigue (RCF) damage of rail materials has become increasingly important since developing effective measures to mitigate RCF damage is crucial. This study focuses on exploring the influence of full slip and partial slip contact modes at the wheel-rail contact patch on the RCF damage behavior and the shakedown limit of the pearlite rail material through wheel-rail RCF rolling-sliding tests. Firstly, based on the wheel-rail adhesion-creep curves in dry, water and oil environments, the creepage required to achieve full slip during the rolling-sliding tests was determined. Then, rolling-sliding tests under full slip contact with different adhesion coefficients were carried out in a dry atmosphere and with the assistance of a third body medium (i.e., oil and water), respectively. Meanwhile, rolling-sliding tests under partial slip contact with the similar contact parameters were performed in a dry atmosphere. The results indicated that RCF damage and wear rates of the rail material under a full slip contact with an adhesion coefficient below the saturation peak on the adhesion-creep curve were significantly less than those under partial slip contact with similar contact parameters. Moreover, under full slip contact with an adhesion coefficient below the saturation peak on the adhesion-creep curve, the pearlite rail materials could exhibit a higher shakedown limit. Furthermore, the influence of full slip and partial slip contact on wheel-rail contact behavior was further analyzed using finite element simulations. Finally, a novel friction modification strategy to mitigate RCF damage and wear of rails was proposed. By applying a specific low-coefficient friction modifier to the wheel-rail interface, the operation of powered wheelsets under controlled creepage conditions that reach the threshold of full slip contact at the wheel-rail contact interface could be employed to achieve the desired adhesion coefficient. Thus, this approach could ensure that the achieved adhesion coefficient met the on-site target adhesion force while reducing RCF damage and wear of rail materials.