Marine coatings protect submerged surfaces from the negative effects of biofouling. In this work, we demonstrate a new method to prepare self-stratified, amphiphilic glycidyl-carbamate (GC)-based (epoxy urethane-based) coatings (AmpSiGC coatings) that have fouling-release properties making them suitable for marine use. The prepared coating systems are unique and durable in character as the bulk coating takes advantage of both epoxy and urethane functionalities while the surface is comprised of both hydrophilic and hydrophobic domains, granting it an amphiphilic characteristic. The experimental approach aimed to evaluate several factors that influence coating performance, including molecular weight of poly (ethylene glycol) (PEG) and PDMS moieties, ratio of hydrophobic (PDMS) and hydrophilic (PEG) components in the system, and the effect of different curing agents. The results demonstrated that polymeric chains of 10,000 $${\overline{M} }_{n}$$ PDMS and 750 $${\overline{M} }_{n}$$ PEG at 10–15 wt.% each offer substantially improved or comparable fouling-release performance in comparison to commercial marine coatings. This paper reports on the facile synthesis and characterization of the GC resin and GC prepolymers using FTIR and epoxy titrations; surface characterization of the coatings using ATR-FTIR, XPS, and AFM; and fouling-release assessment of the surfaces using laboratory biological assays with the barnacle Amphibalanus amphitrite, the algae Ulva linza and Navicula incerta, and the bacteria Cellulophaga lytica. Several of the AmpSiGC coatings exhibited promising performance, which were better or comparable to the internal and commercial reference coatings. The performance of the systems was dependent on all of the factors considered in this study.