Horatio Wills was a son of Sarah Wills and her husband, convict Edward Spencer Wills, who established a successful merchant business in George Street Sydney, early in the nineteenth century. Edward Wills died before Horatio was born, and Sarah married George Howe, the founder and publisher of the Sydney Gazette, and the Gazette for some years occupied premises that had belonged to the Wills's business.

Horatio was apprenticed as a printer at the Gazette under his step-brother, Robert Howe. He and Howe quarrelled, and Wills left his position around the time of Howe's death in 1829, but he returned to the Gazette as its printer between March 1832 and June 1833. Wills founded, printed and edited the journal The Currency Lad in 1832/3, which was published jointly with the executors of Robert Howe's estate.

Wills was a pioneering pastoralist near Ararat, in Victoria, and owned a property near Geelong in the 1850s. He was a Member of the Victorian Legislative Council in 1855, and elected a Member of the first Legislative Assembly of Victoria in 1856.

Wills was killed by members of a local Aboriginal group while on an expedition to take up land for settlement in the Rockhampton, Queensland District.