Wettability is a key parameter that affects the petrophysical properties of reservoir formations. The objective of the present work is to investigate the influence of the temperature and pressure on the wettability in crude oil-brine-rock systems. Using a captive droplet method, the contact angle results of seven minerals and two rock core samples over a range of pressures and temperatures are reported. The data show that raising the pressure from 10 to 70 MPa has no discernible effect on the contact angle, regardless of the mineral type. However, the effect of the temperature on the contact angle depends upon the primary wettability types of the minerals. For water-wet mineral surfaces, the temperature has a notable impact on the measured contact angles (i.e., the contact angle decreases with an increasing temperature), but for neutral-wet or oil-wet samples, the influence of the temperature on the measured contact angles is relatively weak. To explain the behavior of the wettability as a function of the temperature, a mathematical calculation is completed on the basis of the Derjaguin-Landau-Verwey-Overbeek theory. The calculation results show good consistency with the experimental measurements.