The Maverick brothers were poker players from Texas who traveled the American Old West by horseback and stagecoach, and on Mississippi riverboats, constantly getting into and out of life-threatening trouble of one sort or another, usually involving money, women, or both. They would typically find themselves weighing a financial windfall against a moral dilemma. Their consciences always trumped their wallets since both Mavericks were intrinsically ethical.

When Garner left the series after the third season due to a legal dispute, after which Garner began a successful movie career, Roger Moore was added to the cast as cousin Beau Maverick. As before, the two starring Mavericks would generally alternate as series leads, with an occasional "team-up" episode.

Partway through the fourth season, Robert Colbert replaced Moore and played a third Maverick brother, Brent. No more than two series leads (of the four total for the run of the series) ever appeared together in the same episode, and most episodes featured only one. All two-Maverick episodes included Jack Kelly as Bart Maverick. For the fifth and final season, the show returned to a "single Maverick" format as it had been originally in the first eight episodes, with all the remaining new episodes starring Kelly as Bart. The new episodes, however, alternated with reruns from earlier seasons starring Garner as Bret.

Budd Boetticher directed several of the early episodes of the first season until sharply disagreeing with Huggins about Maverick's philosophy, which resulted in Boetticher assigning Bret Maverick's scripted lines to supporting characters and filming the result, thereby attempting to change the whole series by making Maverick into a standard Western hero as found in the earlier Boetticher-directed series of theatrical films starring Randolph Scott. Robert Altman wrote and directed the episode entitled "Bolt from the Blue", starring Roger Moore, in the fourth season, with a couple of scenes later purloined for the subsequent Mel Gibson movie version.

Sir Roger George Moore KBE (14 October 1927 – 23 May 2017) was an English actor best known for playing British secret agent James Bond in seven feature films from 1973 to 1985, beginning with Live and Let Die. His most notable television role was playing the main character, Simon Templar, in the British television series The Saint from 1962 to 1969. He also had roles in some American television shows and films in the late 1950s and early 1960s, including replacing James Garner and portraying Beau Maverick in the Maverick series in 1960–1961. Moore starred with Tony Curtis in The Persuaders television series in 1971 to 1972, and had roles in several theatrical films in the 1970s and 1980s.