Manuel Amador was born to José María Amador and Mercedes Guerrero y Córdoba. He studied medicine at the University of Cartagena and emigrated to Panama in 1855. That year the Trans-Isthmic Railroad opened, bringing relative prosperity to this department, which became a crucial juncture for North American people and merchandise during the California gold rush. Amador was hired as a doctor for the Railway Company, the company that years later would push for the separation of the Isthmus from Colombia. His marriage to María de la Ossa tied him to the prosperous and powerful business families of the isthmus.
Around the 1860s, Amador appeared on the local political scene within the Conservative Party, and he became recognized upon being appointed to important public positions: Congressional representative for the province of Veraguas; First Designate of the Sovereign State of Panama in 1866; President of Panama in 1867, although he could not hold office; Acting Civil and Military Chief in 1886; and assistant to the governor Victor Salazar during the Thousand Day War, who proposed that he be a member of the Senate from 1902 to 1903, a position that was taken from him by Vice President Marroquín.
His militant conservativism and family ties may explain why he played such a key role in the crucial moment when the Isthmus decided to separate from Colombia.