We use ultrahigh resolution, tunable, vacuum ultraviolet laser-based, angle-resolved photoemission spectroscopy (ARPES), temperature- and field-dependent resistivity, and thermoelectric power (TEP) measurements to study the electronic properties of WTe2, a compound that manifests exceptionally large, temperature-dependent magnetoresistance. The Fermi surface consists of two pairs of electron and two pairs of hole pockets along the X−Γ−X direction. Using detailed ARPES temperature scans, we find a rare example of a temperature-induced Lifshitz transition at T≃160  K, associated with the complete disappearance of the hole pockets. Our electronic structure calculations show a clear and substantial shift of the chemical potential μ(T) due to the semimetal nature of this material driven by modest changes in temperature. This change of Fermi surface topology is also corroborated by the temperature dependence of the TEP that shows a change of slope at T≈175  K and a breakdown of Kohler’s rule in the 70–140 K range. Our results and the mechanisms driving the Lifshitz transition and transport anomalies are relevant to other systems, such as pnictides, 3D Dirac semimetals, and Weyl semimetals.