While searching for the man who framed him for a crime he didn't commit, Harrison Destry (John Gavin) stumbles into a town where an old cell mate of his is being tried for robbery and murder. The outlaw has hidden the loot and offers to reveal the location to Destry, but instead provides the location to Patience Dailey, a gold digging saloon singer played by Tammy Grimes.

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.

In the Salinas Valley in and around World War I, Cal Trask feels he must compete against overwhelming odds with his brother for the love of their father. Cal is frustrated at every turn, from his reaction to the war, how to get ahead in business and in life, and how to relate to his estranged mother.

Petty con artists Slicker Smith and Herbie Brown mistakenly join the Army evading the cops. The cop chasing them winds up as their drill instructor. A rich young man and his former working class chauffeur are not only in the same unit, they're vying for a pretty girl who seems attracted to both.

To investigate a gold-shipping scam, a postal inspector goes undercover and tries to infiltrate the gang he believes is responsible.

Retired hockey player Johnny Hansen, in order to make money to enlarge his chicken farm, returns to the game and leads his team into the championship series. Just before the series starts, he is offered a bribe to throw the games but refuses. An attempt is made on his life which results in Bobby, the team's mascot, being injured. Written by Les Adams

Ferguson is a rough-and-tumble hockey player who discovers that his chosen profession is nothing more than a racket, a plaything for game-fixing racketeers. When his brother is killed in a highly suspicious accident, Ferguson and team trainer Holland join forces to bring the killers to justice.