Henry Keyes spent his formative years in Vershire, Vermont, before relocating to Newbury at age 15, where he engaged in business activities. He established a store with his brother, Freeman, in 1831, marking the beginning of a multifaceted career. Keyes made significant contributions to the railroad industry, serving as an incorporator and president of the Connecticut and Passumpsic Rivers Railroad, and completing a crucial connection to the Grand Trunk Railway. His business acumen extended to various ventures, including hotels, mines, and railways, where he held leadership positions. Additionally, Keyes was deeply involved in agriculture, owning a farm and serving as president of the Vermont State Agricultural Society. His educational involvement included serving as a trustee for Norwich University.

Henry Keyes combines a deeply rooted commitment to regional economic development with a strategic blend of business acumen and political leadership. His support for railroads and agriculture reveals a calculated effort to balance industrial progress with local interests. Keyes's approach often shows an unexpected convergence with opposing factions, suggesting a highly localized and ideologically agile political strategy.