Casey in transporting train dispatcher Sam Wilson to Laramie to stand trial for murder. Only the marshal taking him there is the brother of the murdered man and has a reputation of arriving with dead prisoners.
Alice Jones convinces Casey that the risks are too great for a family man and that he should take the desk job as District Manager. Only when the Cannonball's new engineer refuses to run a rescue mission, Jones now must decide which job he'll take.
The Cannonball breaks down, running out of water in the middle of Apache territory. Casey's friend Mallory must decide if he will overcome his fears and risk his own life to save the life of the man who fired him.
Casey begins to suspect that a man who has hired the Cannonball Express to shuttle his wedding party has other motives when he wants to stop and pick up some suspicious looking men on the way.
Casey takes the Cannonball on an emergency mission of transporting nitroglycerine to the scene of a mining accident, only on board the train is a man with a different timely mission.
Expensive raw silk is on the Cannonball but has become the target of thieves who plan on staging a crash to steal the cargo.
While Casey was gone, the Express was robbed two times, both times with his friend Earl Bonner at the controls. But Casey has a hard job in wanting the truth while staying true to his old friend.
Casey Jr. finds a map on the Cannonball Express after a gunfight on board. But he's not the only one interested in the map.
Bank robbers hijack the Cannonball Express and when it's discovered that Alice Jones is on the train, Casey is threatened with her death if he doesn't do what they want.
Casey must get a sailor who has smallpox to a hospital. It turns out to be a lot harder than that when quarantined passengers attempt to leave the train and citizens along the route refuse to let the infected train stop.
Jones is suspended during an investigation to determine if sparks from his engine destroyed a farmer's crops. That doesn't stop Casey from doing some investigating of his own.
A witness of a recent railroad accident is on her way to Denver, in the company of a U.S. Marshall when shots are fired as the Cannonball enters into a tunnel.
Casey has no idea that the drifter who just saved the Cannonball and has been hired in the rail yard is being threatened by a blackmailer.
The Mexican government has a very special shipment riding on the Cannonball Express, Maximillian's crown jewels. Only the Secret Service agent onboard is an impostor intent of stealing the treasure.
Morgan's Marauders plan on raiding Dover City and Casey is ordered to purposely wreck a train which has on it the Marshal and his posse.
Casey must work quickly to rescue the people of Valley Junction from flood waters caused by the dam that is about to break due to a fierce storm.
Casey must take on the position of Sheriff after the sheriff of Bitter Creek is killed by a gang dead set on revenge.
Unknown to Casey is a woman hiding in the cab who has her sites set on robbing the strong box that is headed for the Midvale bank.
When cattlemen unwilling to share their land threaten the immigrants working on the railroad, Casey and crew come to their aid.
Casey and his family are held hostage when two fugitives from the law break into his house. When one becomes sick, Casey tries to persuade the other to help him instead of letting him die.
A young woman is suddenly attacked with a severe case of appendicitis while riding on The Cannonball Express and her one chance of survival is Doc Baily, a prisoner on the train on his way to trial for murder.