Nature uses protein structure to manipulate the properties of water by altering its local environment, but subtle changes in these structures can dramatically influence function. Here, a simple synthetic analog is demonstrated, a statistical copolymer of hydroxyethyl acrylate and n-octadecyl acrylate (HEA–ODA) with 21.3 mol% ODA, that generates a hydrogel in water. The crystallization of the ODA, whose nanodomains act as effective crosslinks, provides a simple route to manipulate the nanostructure through zone annealing without significantly altering the swelling ratio (1.38 to 1.22) of the hydrogel. Despite the identical average composition, changes in the nanostructure induced by zone annealing leads to significant differences in the inhibition of water crystallization within the hydrogels under supercooled conditions with the unfrozen water fraction varying between nearly 18 and 99%. Decreasing the average spacing between crystalline nanodomains leads to increased efficacy of the ice inhibition. However, the morphological details appear to be important as the average number of water molecules confined in a hypothetical square lattice based on the average interdomain spacing and average ODA nanodomain size does not appear to directly scale with the antifreeze capabilities. These results demonstrate control of water crystallization at supercooled temperatures within hydrogels without fluorinated hydrophobic moieties through manipulation of the nanostructure to confine the water.