Small-hole structures, such as the millions of fastener holes found on aircraft, are typical stress-concentration structures prone to fatigue failure. To further improve the strengthening process of this small-hole structure, we make up for the limitations of laser shock processing (LSP) of small holes by combining it with the ultrasonic extrusion strengthening (UES) process to form a new strengthening method—laser shock and ultrasonic extrusion strengthening (LUE). The influence of the LUE process sequence and process parameters on residual stress distribution was studied through FEM, and the gain of fatigue life of specimens after LUE strengthening was also explored through tests. The results show that when using LUE technology, the friction force decreases with the increase in amplitude and decreases by 3.2% when the amplitude is maximum. The LUE process eliminates the thickness effect generated by LSP, which can achieve good stress distribution of small-hole components under smaller laser shock peak pressure, and reduces equipment power. LUE can significantly improve the fatigue life of small-hole components, and the maximum fatigue life gain can be up to 310.66%.