We report the effects of use and placement of amphiphilic end groups as a valuable tool to achieve significant changes in the thermoresponsive properties of diblock copolymers without the need to resort to compositional changes. We prepared diblock copolymers of di(ethylene glycol) methyl ether methacrylate and oligo(ethylene glycol) methyl ether acrylate with phenyl dithioester and carboxylic acid chain ends and compared the effects of placement of these amphiphilic chain ends on the cloud points of the copolymers. All the copolymers were high molecular weight (greater than 20 kDa) with a polydispersity between 1.1 and 1.2, and the cloud points were measured by UV–vis spectrophotometry and reported as the temperature at 50% normalized transmission. The thermoresponse showed a significant dependency on end group placement, reaching as much as a 28 °C difference in measured cloud point simply by exchanging end group placement rather than compositional changes. The effect is attributed to changes in the solvation and mobility from chain end placement affecting the degree of association of the chains. The underlying effect is due to the hydrophilic/hydrophobic balance in combination with the use of amphiphilic chain end placement that can be applied to copolymers with different blocks at the chain ends. This work shows that substantial changes in thermo-response properties can be achieved by re-arranging monomer components rather than changing monomer composition. This may have value in biomedical materials where the range of acceptable monomers is limited.