Accurate temperature measurements in flow lines are critical for many industrial processes. It is normally more a rule than an exception in such applications to obtain water flows with inhomogeneous temperature distributions. In this paper, a number of comparisons were performed between different 100 ohm platinum resistance thermometer (Pt-100) configurations and a new speed-of-sound-based temperature sensor used to measure the average temperature of water flows with inhomogeneous temperature distributions. The aim was to achieve measurement deviations lower than 1 K for the temperature measurement of water flows with inhomogeneous temperature distributions. By using a custom-built flow injector, a water flow with a hot-water layer on top of a cold-water layer was created. The temperature difference between the two layers was up to 32 K. This study shows that the deviations to the temperature reference for the average temperature of four Pt-100s, the multisensor consisting of nine Pt-100s, and the new speed-of-sound sensors are remarkably lower than the deviation for a single Pt-100 under the same conditions. The aim of reaching a deviation lower than 1 K was achieved with the speed-of-sound sensors, the configuration with four Pt-100s, and the multisensor. The promising results from the speed-of sound temperature sensors open the possibility for an integrated flow and temperature sensor. In addition, the immersion depth of a single Pt-100 was also investigated at three different water temperatures.