In this work, a series of amphiphilic lignin-acrylamide copolymers was synthetized via a "grafting from"approach using α-butoxylated organosolv lignin. This lignin is obtained in high yield via a mild organosolv extraction with butanol and contains a well-defined modified β-O-4 structure that allows for site-selective modification of the primary alcohol in the γ-position. The modified lignin was then used as a precursor of amphiphilic copolymers by reaction with acrylamide, either via free radical polymerization or via atom transfer radical polymerization after converting the lignin into a suitable macroinitiator. The effect of the synthetic method and acrylamide/lignin ratio on the final properties was studied and compared. Relevant solution properties, in particular, shear viscosity and interfacial and surface tension, showed that different synthetic methods and polymer compositions allow a tuning of the solution behavior toward specific potential applications, such as emulsion stabilization or enhanced oil recovery. Furthermore, it was preliminarily shown that the obtained polymers may potentially display low cytotoxicity, further increasing the possibilities for applications.