After studying law, Hassenpflug entered the Hesse-Kassel civil service. In 1832 he was named minister of the interior and of justice in Hesse-Kassel and set to work to undermine the state's liberal 1831 constitution. Dismissed in 1837, he headed the administration of Hohenzollern-Sigmaringen (1838–39), served as civil governor of Luxembourg (1839–40), and became a Prussian civil servant (1841–50).

Recalled to Hesse-Kassel by the elector Frederick William I in 1850, he resumed his struggle against the constitution. Because he was opposed by all social classes and even by the army, he resolved to rely on support from Austria. Hassenpflug persuaded Frederick William to take Hesse-Kassel out of the Prussian-sponsored Erfurt Union of North German states, but his call on Austria for armed intervention against Hessian liberals almost led to war between Austria and Prussia until the situation was resolved by the Punctation of Olmütz (November 1850). Hassenpflug was finally dismissed from his high offices in 1855. By the time he died in 1862, the 1831 constitution had been largely restored.