The series initially starred veteran movie supporting actor Ward Bond as the wagon master, later replaced upon his death by John McIntire, and Robert Horton as the scout, subsequently replaced by lookalike Robert Fuller a year after Horton had decided to leave the series. The series was inspired by the 1950 film Wagon Master directed by John Ford and starring Ben Johnson, Harry Carey Jr. and Ward Bond, and harkens back to the early widescreen wagon train epic The Big Trail starring John Wayne and featuring Bond in his first major screen appearance playing a supporting role. Horton's buckskin outfit as the scout in the first season of the television series resembles Wayne's, who also played the wagon train's scout in the earlier film.

The tale of trail boss Gil Favor and his trusty foreman Rowdy Yates as they drives cattle across the old west. Along the way they meet up with adventure and drama.

An innocent fugitive from the law lives in the wilderness with a grizzly bear companion and helps passers-by in the forest.

Indian scout Tom Jeffords is sent out to stem the war between the American settlers and Apaches in the late 1870s Arizona. He learns that the Indians kill only to protect themselves, or out of retaliation for white atrocities.

Lin McAdam rides into town on the trail of Dutch Henry Brown, only to find himself in a shooting competition against him. McAdam wins the prize, a one-in-a-thousand Winchester rifle, but Dutch steals it and leaves town. McAdam follows, intent on settling his old quarrel, while the rifle keeps changing hands and touching a number of lives.

Hollywood, 1930s. Tod Hackett, a young painter who tries to make his way as an art director in the lurid world of film industry, gets infatuated with his neighbor Faye Greener, an aspiring actress who prefers the life that Homer Simpson, a lone accountant, can offer her.

Will Lockhart arrives in Coronado, an isolated town in New Mexico, in search of someone who sells rifles to the Apache tribe, finding himself unwillingly drawn into the convoluted life of a local ranching family whose members seem to have a lot to hide.

There's a deficit of good, honest women in the West, and Roy Whitman wants to change that. His solution is to bring a caravan of over 100 mail-order brides from Chicago to California. It will be a long, difficult and dangerous journey for the women. So Whitman hires hardened, cynical Buck Wyatt to be their guide across the inhospitable frontier. But as disaster strikes on the trail, Buck just might discover that these women are stronger than he thinks.

Gunslinger Annie Oakley romances fellow sharpshooter Frank Butler as they travel with Buffalo Bill's Wild West Show.

In 1866, a new gold discovery and an inconclusive conference force the U.S. Army to build a road and fort in territory ceded by previous treaty to the Sioux...to the disgust of frontier scout Jim Bridger, whose Cheyenne wife led him to see the conflict from both sides. The powder-keg situation needs only a spark to bring war, and violent bigots like Lieut. Rob Dancy are all too likely to provide this. Meanwhile, Bridger's chance of preventing catastrophe is dimmed by equally wrenching personal conflicts. Unusually accurate historically.

It's 1876 and all the Indians are at peace except the Comanches lead by Black Cloud. When Black Cloud wipes out a town, only six soldiers are left and they head for the nearest fort. In the desert they are reinforced by members of a stagecoach and find some water at a deserted mission. Pinned down by Black Cloud they send an Indian boy who was Black Cloud's prisoner on to the fort while they try to bargain with Black Cloud whom they learn is without water.

A cowboy is hired by a stagecoach boss to stop the railroad reaching his territory and putting him out of business. He uses everything from Indians to dancehall girls to try to thwart the plan. But the railroad workers, led by a female sharpshooter and an ambitious salesman, prove tough customers.

During the Civil War, in Wyoming, horse dealers Joan Britton and Stephen Cook are competing to supply the Union Army with horses. A Cherokee is in the area to stir up the Sioux against the Union just as Cook decides to steal a herd of Sioux horses. Ex-army doctor Jonathan Westgate opposes Cook’s unscrupulous methods as well as being Cook’s rival for the affections of Joan. It seems Westgate is the only one able to prevent a new Indian war.

A cavalry officer, the sole survivor of an Indian attack, and a wagon load of prisoners travel through hostile Indian country.

In the Canadian mountains, a trapper goes on the run accused of a crime and is pursued by a rugged and determined lawman of the Royal North-West Mounted Police.

A gambler is thrown out of a western town, but returns when the town is suddenly threatened by a band of marauding Apaches.

Hodiak, Brian, Derek and Teal have just been released from prison. They return to Tomahawk Gap, now a ghost town, to retrieve the money that they stole and was buried by a partner somewhere in the town. While hunting, the Indians attack, and a life and death battle ensues.

A young cavalry doctor treats very sick Indians against orders, whom are forced to stay on unhealthy land, which could lead to a war.

A housewife flees from a policeman's killer on the road between Phoenix and Denver.

Young Indian brave White Bull captures and tames a wild stallion and names him Tonka. But when White Bull's cruel cousin claims Tonka for his own and mistreats the horse, White Bull sets him free. Tonka finally finds a home with Capt. Keogh and the 7th Calvary, and in 1876, rides into the Battle of Little Big Horn with General Armstrong Custer, becoming its only survivor.