The aim of the present work was to investigate in detail the influence of running-in with acetylacetone on the friction behavior of 5CB liquid crystal between steel surfaces. Friction tests were carried out using a sliding ball-on-disk tribometer. The coefficient of friction (COF) decreased significantly after a running-in process with acetylacetone. Tribochemical reactions between steel and acetylacetone generated Fe(acac)3 and groove-structured wear on the ball. Their synergistic effect is the reason for the ultralow friction, and without either one, the COF increases. Special attention was given to the rheological behavior of 5CB. Shear history has a significant influence on the viscosity and storage moduli of 5CB. In addition, the COF under the same low speed decreased by 37% after a friction test at higher speed. The possible mechanism is discussed, and an in-depth understanding of this tribological system is needed to develop possible future applications.