In tribo-systems, tribological behavior is influenced by a combination of several mechanisms. Among them, plastic deformation mechanisms (PDM) and tribo-chemical reactions (TCR) are particularly significant. The manuscript explores the role of these fundamental mechanisms during dry sliding of Ti6Al4V-pin against a SS316L-disk. PDM was controlled by changing the sliding speed (0.01-1.5 ms−1). To explore the interdependence of TCR sub-mechanisms, namely the formation of mechanically mixed layer (MML) and tribo-oxidation, the pin diameter was varied (2.1, 4.6, and 6.6 mm) while maintaining a constant vacuum environment and contact pressure. At low sliding speeds (0.01-0.3 ms−1), the high wear rate and coefficient of friction (CoF) is due to the dominance of PDM, enabled by adiabatic shear banding (ASB). Within the sliding speed range of 0.3–0.7 ms−1, a durable and wear-resistant MML forms on the pin surface incorporating Fe transferred from the disk. As the MML attains its highest stable thickness (≈ 51 μm, at 0.7 ms−1), the lowest values of wear rate (18.15 × 10−4 mm3/Nm) and CoF (0.324) is observable. Above 0.7 ms−1, thermally-induced phase transformation-assisted material softening leads to substantial increase in wear rate and CoF. The case is otherwise for the smallest pin (2.1 mm) sliding at 1.5 ms−1. As sliding speed increases, wear transitions from adhesion to mild abrasion and then to severe adhesion.