We propose a new pretreatment method on fiber preforms by loading deuterium (D2), pre-irradiation, combined with thermal annealing. The effect of the pretreatment condition on the optical loss at 1200 nm and a laser slope efficiency of ytterbium-doped silica fibers (YDFs) before and after γ-radiation was comparatively investigated. The related mechanism was revealed by combining the optical absorption, continuous wave electron paramagnetic resonance (CW-EPR), Raman, and Fourier transform infrared (FTIR) spectroscopies. A laser experiment shows that the radiation resistance of YDFs can be significantly improved by the pretreatment on a fiber preform. Also, this new pretreatment method has no obvious negative impact on the laser performance of non-irradiated YDFs. Furthermore, the vacuum experiment confirms that the YDF obtained by this method, named pretreated YDF, may have a long-term radiation stability when it is used in a vacuum environment (such as space). CW-EPR spectra show that the formation of color centers was effectively inhibited in pretreated YDF, which is correlated with the decrease of color center precursor and the existence of the deuterium radical as confirmed by Raman and FTIR spectra.