Understanding defect diffusion kinetics in a strain field is essential for multiscale modeling of UO2 microstructure evolution, particularly in the case of creep, swelling, crack, etc. Although the diffusion kinetics of point defects in UO2 is well explored both experimentally and theoretically, the kinetics under strain conditions is not well understood. In the present study, the diffusion of oxygen monovacancy in UO2 subjected to uniaxial tensile strain as much as 3% in the directions of <100>, <110>, and <111> is investigated by means of molecular dynamics (MD) simulations in the temperature range of 600–1000 K. The results show that in the case of strain in <100> direction, diffusivity decreases with tensile strain, especially at high temperatures above 700 K. In contrast, diffusion is promoted with stretching in <110> and <111> directions. It is assumed that this may be the combined result of independent variation of migration energy (Em) and pre-factor (D0), according to the Arrhenius equation. Further investigations are made with nudged elastic bands (NEB) calculations for a better interpretation of the effect of directional strain on migration energy. It is found that the effect is anisotropic, and the variation of Em is in good agreement with that of MD calculations. Stretching along the <100> direction results in the decrease of Em in all three directions, with <100> the most profound. Stretching in <110> and <111> directions exert negligible effect. The present study provides insights into the effect of strain on the diffusion of oxygen vacancy in UO2, however, further research is needed for the effect of arbitrary strain on poly-crystalline UO2.