When used in radiation environments, such as space, nuclear reactors, and large accelerators, fibers undergo significant parameter changes due to their interactions with radiation, including radiation induced attenuation, radiation induced refractive index changes, radiation induced lifetime changes, and radiation induced luminescence, which can severely degrade the performance of the fiber laser systems. Here, the response characteristics of Yb-doped fiber lasers to gamma-ray radiation are investigated through experiments and simulations. The performance variations of various fiber components after gamma radiation, including passive fiber, pump combiner, fiber Bragg grating and active fiber, are studied and compared with those under an cumulative total dose up to 1000 Gy. And, the experiments show that in a fiber laser system, the active fiber is the most sensitive part to gamma radiation, while the response of various passive fiber components can be ignored. Then, the influences of cavity configuration parameters, such as pump scheme and active fiber length, on the response of fiber lasers are explored through a series of radiation experiments. The results indicate that compared with forward pumping, backward pumping scheme helps to improve the ability of fiber lasers to resist radiation. Moreover, when operating under radiation conditions, lasers with relatively short active fibers exhibit smaller power drops. Besides, corresponding simulations are carried out using the previously developed multi-physics thermal model considering hundred-watt level Yb-doped fiber lasers, and the results are consistent with the experiments. This study has guiding significance for the design optimization of fiber laser systems operating in radiation environments.