The vegetated region is known as the “hot zone” for the exchange of substances in river systems, which causes an uneven pressure distribution at the sediment–water interface (SWI) and then forms hyporheic exchange (HE). However, as a common form of plant survival, the impact of vegetation patches on HE has received little research attention. In this study, laboratory experiment and numerical simulations were conducted to explore the effects of solid volume fraction within the patch (φ), the overlying water average velocity (U), and the streamwise distance of the patches (Sx) on HE. The results showed that the pressure along the SWI caused the spatial–temporal characteristics of HE at the vegetation patch (VP) scale and vegetation patch group (VG) scale. At the VP scale, the HE depth was influenced by φ, U, and Sx in increasing order, and increased with the increase in these values within a certain range. At the VG scale, the HE depth was positively correlated with φ and U and negatively correlated with Sx, and the spatial characteristics of HE were larger at this scale than at the VP scale. The HE flux was linearly related to φ and power functionally related to U. There was an asymptotic behavior of the effect of Sx on the HE flux, which means that the rate of change of the HE flux progressively decreases with Sx. The HE volume was influenced by Sx, φ, and U in increasing order and was positively correlated with all of these parameters. Based on the flow blockage parameter, Reynolds number (Re), and Sx, a prediction model of HE flux was developed. The results of this study provided further understanding of the role of vegetation patches in driving the HE process and may serve as a reference for vegetated river benthic habitat restoration.