Polyacrylamide-based (PAM) polymers are the most widely used synthetic water-soluble polymer so they are applied in a range of industries. However, they suffer from a number of limitations which requires the development of synthetic routes that can accurately control polymer structure and hence function. This study describes a carbodiimide mediated coupling reaction (CMC) that is used to generate modified polyacrylamide (PAM) including hydrophobically modified water-soluble polymers (HMWSP). The reaction proceeds efficiently in water and does not require organic solvents or high temperatures. The approach is flexible due to the efficiency of the CMC reaction allowing for accurate control over polymer structure and function. This is confirmed using acid-base titration, spectroscopy, viscometry, and rheology. The viscosity of the polymers varies over a broad range with those containing larger hydrophobic group (dodecyl) showing the highest viscosity. The hydrophobicity of the pendent group determines how it influences viscosity and using this new synthetic approach polymer with the same molecular weight can be compared. Linear hydrocarbon pendent groups are more hydrophobic than the cyclic versions resulting in higher viscosity. However, the spatial arrangement of the pendent group (linear or cyclic) also affects the viscosity at higher pendent group contents. The number of modified PAMs that can be generated is expansive because the approach works with a number of different functional groups and base polymers.