The control of biointerfacial interactions is of outstanding interest in a broad range of biomedical applications, ranging from biosensors to implantable medical devices. Here, a fundamental requirement is often the reduction or prevention of non-specific biological interactions, so-called biofouling, ranging from protein adsorption to microbial and cell attachment. While a range of graft polymer-based technologies have been developed aimed at achieving this goal, there are limited options due to the need for suitable functional groups on the device surface in most cases to covalently attach polymers. We have developed photo-reactive copolymers of 2-hydroxypropyl acrylamide and N-benzophenone acrylamide. These polymers were deposited from solution by casting or spin coating and crosslinked under UV irradiation. This simple process leads to covalent anchoring of the coating on a substrate material without the need for specific functional groups. In this study, coatings deposited on different substrate materials were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), UV-vis spectroscopy, infrared spectroscopy (ATR-FTIR), profilometry and contact angle measurements. Furthermore, the attachment of primary human foreskin fibroblasts and Escherichia coli was investigated over a period of up to 24 hours. Our results demonstrate the ability to adjust the coating properties such as the modulus of the crosslinked coating as well as the cell and bacterial attachment by adjusting the molar ratio of the benzophenone component in the copolymer. Crosslinked coatings containing 1 mol% of this component showed excellent prevention of biofouling. It is expected that the coating method will be translated into biomedical device applications due to the simplicity and effectiveness of the copolymer approach.