Ytterbium-doped silica fiber (YDF) is the core component of high-power fiber lasers, the core material of which is ytterbium-doped silica glass (YDG). The performance of YDF is closely related to the properties of YDG. To achieve high power and high beam quality laser output, in addition to effectively controlling the loss of YDF, the following two prominent problems need to be solved. On the one hand, to suppress the nonlinear effects, it is necessary to increase the doping concentration of ytterbium ions (Yb3+) in the YDG, thus to use as short as possible and larger mode-field-area YDF. On the other hand, to achieve high beam quality, it is necessary to reduce the numerical aperture of the inner cladding as much as possible, that is, to reduce the refractive index difference between the YDF core material and the cladding one. Therefore, in the core composition design of YDF, especially the high-power one, it is necessary to co-dope Al, P, Ge, F, and B elements to obtain ideal refractive index and spectral properties to meet the final use requirements. In addition, the preparation of YDF mainly includes two temperature-related steps: preform deposition and drawing process. During this process, YDF will undergo a thermal process of heating and cooling. The change in its thermal history will not only cause changes in Yb3+ absorption coefficient and the absorption peak position, but also will affect the refractive index of the cladding and core materials to varying degrees, leading to changes in the numerical aperture of YDF, thereby influencing the laser performance of YDF. Based on this, this chapter systematically elaborates the effects of co-doping elements and thermal history on the physical and optical properties of YDG. The corresponding mechanisms from the atomic microscale has been also analyzed by the Fourier transform infrared spectroscopy (FTIR), Raman, nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and other structural analysis techniques.