Ultrasonic welding of titanium alloy Ti6Al4V to carbon fibre reinforced polymer (CFRP) at 20 kHz frequency requires suitable welding tools, so called sonotrodes. The basic function of ultrasonic welding sonotrodes is to oscillate with displacement amplitudes typically up to 50 µm at frequencies close to the eigenfrequency of the oscillation unit. Material properties, the geometry of the sonotrode, and the sonotrode tip topography together determine the longevity of the sonotrode. Durable sonotrodes for ultrasonic welding of high-strength joining partners, e.g., titanium alloys, have not been investigated so far. In this paper, finite element simulations were used to establish a suitable design assuring the oscillation of a longitudinal eigenmode at the operation frequency of the welding machine and to calculate local mechanical stresses. The primary aim of this work is to design a sonotrode that can be used to join high-strength materials such as Ti6Al4V by ultrasonic welding considering the longevity of the welding tools and high-strength joints. Material, sonotrode geometry, and sonotrode tip topography were designed and investigated experimentally to identify the most promising sonotrode design for continuous ultrasonic welding of Ti6AlV4 and CFRP. Eigenfrequency and modal shape were measured in order to examine the reliability of the calculations and to compare the performance of all investigated sonotrodes.