With the assistance of American lobbyist and lawyer William Nelson Cromwell, Bunau-Varilla greatly influenced Washington's decision concerning the construction site for the Panama Canal.

When the New Panama Canal Company sprang up back in his native France, Bunau-Varilla sailed home, having purchased a large amount of stock.

[2] When opponents voiced their interest in constructing a canal through Nicaragua, which was a less politically volatile nation, Bunau-Varilla actively lobbied in the United States, for example by distributing Nicaraguan postage stamps featuring belching volcanos to senators.

[3] Through lobbying of businessmen, government officials, and the American public, Bunau-Varilla convinced the U.S. Congress to appropriate $40 million to the New Panama Canal Company, under the Spooner Act of 1902.

Bunau-Varilla's company was in danger of losing the $40 million of the Spooner Act, and so he drew up plans with Panamanian separatists in New York for secession from Colombia.

By the eve of the planned revolution, Bunau-Varilla had already drafted the new nation's constitution, flag, and military establishment, and promised to float the entire government on his own checkbook.

[6] Bunau-Varilla had received his ambassadorship through financial assistance to the rebels, he had not lived in Panama for seventeen years, and he never returned,[7] leading to the charge that he was "appointed Minister by cable".

He made his fortune during his second stay in Panama from 1886 to 1889, where he ran his own company, Artigue & Sonderegger, together with his brother Maurice, who later became the rich owner of Le Matin, a major Parisian newspaper.