Nitroxide-mediated controlled radical polymerization of 2-hydroxyethyl methacrylate (HEMA) is achieved using the copolymerization method with a small initial concentration of acrylonitrile (AN, 5–16 mol%)) or styrene (S, 5–10 mol%). The polymerization is mediated by N-tert-butyl-N-(1-diethyl phosphono-2,2-dimethyl propyl) nitroxide (SG1)-based BlocBuilder unimolecular alkoxyamine initiator modified with an N-succinimidyl ester group (N-hydroxysuccinimide-BlocBuilder). As little as 5% molar feed of acrylonitrile results in a controlled polymerization, as evidenced by a linear increase in number average molecular weight Mn with conversion and dispersities (Đ) as low as 1.30 at 80% conversion in N,N-dimethylformamide (DMF) at 85 °C. With S as the controlling comonomer, higher initial S composition (≈10 mol%) is required to maintain the controlled copolymerization. Poly(HEMA-ran-AN)s with Mn ranging from 5 to 20 kg mol−1 are efficiently chain extended using n-butyl methacrylate/styrene mixtures at 90.0 °C in DMF, thereby showing a route to HEMA-based amphiphilic block copolymers via nitroxide-mediated polymerization.