Understanding the origin of conformational changes of water-soluble polymers, as affected by external triggers such as temperature or co-solvent addition, is important from a fundamental perspective and for practical applications in responsive materials. Using atomistic molecular dynamics simulations we investigate conformational changes of polypropylene oxide (PPO) in connection to its hydration and capability to form hydrogen bonds upon either a temperature change or addition of another protic solvent (isobutyric acid, IBA) to aqueous solution. We demonstrate that upon addition of a very small amount of IBA, PPO starts to lose hydrogen bonds with water and form stable IBA-PEO hydrogen bonds, which act as a nucleation site for polymer collapse. With further addition of IBA, PPO resides at the IBA/water interface to retain some fraction of hydrogen bonds with water along with IBA-water hydrogen bonds. Unlike PEO where water mostly forms doubly-bonded hydrogen bonds (both hydrogens take part in h-bonding), PPO is hydrated by singly bonded water molecules in its hydration shell. As temperature increases breaking one of the hydrogen bonds in water doubly-bonded with PEO results in singly-bonded water. As a result, PEO retains water in its hydration shell even with a temperature increase and does not collapse upon temperature increase or IBA addition. Furthermore, PEO is capable of maintaining 80% of its hydrogen bonding with water even when it resides in an IBA-rich phase, while PPO retains less than 40% of hydrogen bonds with water while residing at the IBA/water interface. These results illustrate that hydrogen bonding and a polymer’s capability to maintain its hydration shell are the key factors in polymer responsiveness to external triggers, factors that should be taken into consideration upon responsive material design and applications.