The effect of temperatures (1173–1233 K) on the diffusion welding process of the body-centered cubic titanium and the orthorhombic Ti2AlNb interface (B2–O interface) is investigated and analyzed using molecular dynamics. The result shows that Nb and Al atoms are the primary diffusive atoms in the orthorhombic single-crystal Ti2AlNb (O phase), and the diffusive distances of Ti atoms in the Β2 phase are significantly higher than that of Nb and Al atoms in the O phase. The atomic diffusion within the O phase is downhill diffusion, aggregation and interface formation controlled by Nb and Al atoms. As the temperature increases from 1173 to 1233 K, the average diffusion distances during 900 ps of Nb and Al atoms in the O phase are increased from 1.4 nm to 1.9 nm, while those of Ti atoms during 900 ps in the B2 phase are increased from 2.8 nm to 3.3 nm. The modified Arrhenius model considering the pressure effect is established to accurately solve the diffusion activation energy. The significant higher diffusion activation energy, and lower diffusion coefficient and diffusion prefactor of the orthorhombic single-crystal Ti2AlNb result in shorter atomic diffusive distances in the O phase than that of the B2 phase.