The Iron Horse tells the story of the construction of the intercontinental railroad in 19th century America. It follows the hardships and challenges faced by the workers, as well as the conflicts with Native American tribes and the threat of murder. Set in the backdrop of the American Midwest, the film explores themes of love, sacrifice, and the ambition to connect the East and the West.

At the outbreak of the War Between the States, Maryland Calvert is loved by Maj. Alan Kendrick, son of a Virginia general, and Capt. Fulton Thorpe. Nancy, whom Thorpe has loved unwisely, follows him to Washington and commits suicide when she learns he will not marry her; as a result, Alan is forced to request his resignation. When Fort Sumter is fired upon, Alan, who admires Lincoln's principles, joins the Union Army though his father is among the Secessionist leaders; as a result, he is estranged from Maryland. Thorpe, who has joined the Confederacy as a spy, is responsible for Alan's arrest, but Maryland victoriously comes to his aid by ringing the alarm bell.