The film was adapted by Dudley Nichols from the plays The Moon of the Caribbees, In the Zone, Bound East for Cardiff, and The Long Voyage Home by Eugene O'Neill.

A British tramp steamer named the SS Glencairn is on the long voyage home from the West Indies to Baltimore, and then to England during World War II.

Among them is their consensus leader, a middle-aged Irishman named Driscoll; a young Swedish ex-farmer, Ole Olsen; a spiteful steward nicknamed Cocky; a brooding Lord Jim-like Englishman, Smitty; and a burly, thoroughly dependable bruiser, Davis.

On a sultry night in a port in the West Indies, the crew has been confined to the ship by order of the captain, but Drisk has arranged to import a boatload of local ladies.

Reaching England without further incident, the rest of the crew members decide not to sign on for another voyage on the Glencairn and go ashore, determined to help Ole return to his family in Sweden, whom he has not seen in ten years.

The artists insisted on three things to ensure a quality effort: freedom of choice on subject matter, studios on the production lot, and a projection room for viewing rushes.

[6] As Orson Welles did the following year in Citizen Kane, director John Ford shared his title card with cinematographer Gregg Toland in the opening credits for The Long Voyage Home.

Film critic Bosley Crowther of The New York Times liked the screenplay, the message of the film, and John Ford's direction, writing:John Ford has truly fashioned a modern Odyssey—a stark and tough-fibered motion picture which tells with lean economy the never-ending story of man's wanderings over the waters of the world in search of peace for his soul...it is harsh and relentless and only briefly compassionate in its revelation of man's pathetic shortcomings.

But it is one of the most honest pictures ever placed upon the screen; it gives a penetrating glimpse into the hearts of little men and, because it shows that out of human weakness there proceeds some nobility, it is far more gratifying than the fanciest hero-worshiping fare.

[9] The staff at Variety magazine wrote:Combining dramatic content of four Eugene O'Neill one-act plays, John Ford pilots adventures of a tramp steamer from the West Indies to an American port, and then across the Atlantic with [a] cargo of high explosives.