The use of Silane Coupling Agent (SCA) is an important way to improve the joining quality between metal and plastic. However, how to rationally use SCAs is still lack of guidance. We investigate the effect of type of SCA, soaking time of SCA, and combination of SCA on the interfacial features and joint performance of ultrasonically welded AA6061 to CF/PA6. Four SCAs (γ-chloropropyltrimethoxysilane (NQ54), γ-chloropropyltriethoxysilane (KH230), vinyltrimethoxysilane (A171), γ-aminopropyltriethyloxysilane (KH550)) were selected. The results show that the optimal joint strength (30.2 MPa) is obtained when the Al sheets are soaked in KH550 for 3 min. A fully dehydrated condensation reaction occurs between the O—H of the KH550 and the O—H on the aluminum alloy surface, forming plenty of Si—O—Al bonds, which contribute to the improved wetting behavior of liquid PA6 on the aluminum alloy surface. However, the combination of SCAs leads to the consumption of functional groups, hindering the formation of Si—O—Al bonds, and therefore reducing the joint performance.