This study analyzed novel synergistic effects on rejection of arsenic and boron during membrane-based treatment. The effect of pH on rejection was characterized for pure and mixed arsenate, arsenite and borate (As(V), As(III), and B respectively) solutions. The favorable effect of high pH was strongest for B and As(III) due to the similar charge evolution in the pH 7–11 range. While only significant for arsenate, both arsenic species exhibited higher rejections when boron was present. Analysis of watersheds in southern Peru revealed a correlation between arsenic and boron; synthetic river water containing 10 mg/L B (0.97 mmol/L) and 1 mg/L As (0.013 mmol/L) was subsequently tested. Both reverse osmosis (BW30) and nanofiltration membranes (NF90) produced a system permeate that complied with the WHO standards (1 mg/L B and 0.01 mg/L As) above pH 9 in these representative, contaminated waters. The combination of increasing the pH from 7 to 9.5 and the synergistic effect doubled the allowable concentration of As(V) in the feed for BW30 from 0.5 mg/L to 1.0 mg/L. In addition to informing treatment of surface and ground waters, findings could be applied to the reuse of high pH gold cyanidation wastewaters and enhancing boron rejection during seawater desalination.