Crude oil−aqueous solution interactions play an important role in low-salinity waterflooding, but their effects and mechanisms have not been well clarified. Core flooding experiments were first conducted to analyze the effects of crude oil− aqueous solution interactions on enhanced oil recovery (EOR). Then, interfacial tension (IFT) and interfacial dilatational rheology (IDR), total organic carbon (TOC), and ζ-potential measurements were combined to investigate the mechanisms of crude oil− aqueous solution interactions in low-salinity waterflooding. Core flooding results showed that crude oil−aqueous solution interactions are important in low-salinity waterflooding and that adjusting the ionic composition of the aqueous solution could affect EOR. Herein, Mg 2+ and Ca 2+ both had positive effects on EOR, while SO 4 2− showed no positive effect. The IFT and IDR, TOC, and ζ-potential results indicated that the ionic composition of aqueous solutions has a great influence on crude oil−aqueous solution interactions. Thereof, Mg 2+ , Ca 2+ , and Na + preferentially interact with acidic polar molecules and enhance crude oil−aqueous solution interactions, and the intensity is Mg 2+ > Ca 2+ > Na + . SO 4 2− interacts with cations and acidic polar molecules simultaneously, consequently reducing the effects of cations on crude oil−aqueous solution interactions in varying degrees. Therefore, the positive effects of Ca 2+ and Mg 2+ exceed the negative influence of SO 4 2− in CaSO 4 and MgSO 4 , while the negative impact of SO 4 2− outweighs the positive effect of Na + in Na 2 SO 4 .