Roy is a government man assigned to a case of cattle rustling in the part of the country where he grew up, unaware that the leader of the gang is a woman, in fact an old flame.
The Mesquiteers return to Texas after the Civil War to find Army carpetbaggers fighting the local bushwackers. They quickly learn that Capt. Hawks and his men are the culprits and join up with Morgan and his men.
Cholita, after a long absence in Mexico City, is returning home to take up her duties as head of the rancho and, as everyone expects, to marry her childhood sweetheart José. Expectations are somewhat dashed as she shows up with Fernando to whom she is engaged. This makes José and Cholita's uncle more than a little bit put out as Fernando is not only not a Mexican, he is also a city slicker afraid of the country.
To fight a poisonous weed, ranchers are burning their land. Gene is the Inspector brought in and he recommends spraying. The spraying goes well until the Larabee ranch is reached. When Larrabee refuses to allow the equipment on his land, Gene has it sprayed by airplane. Cattle must stay off recently sprayed land and when a Larrabee man shoots down the plane, the crash sends the cattle stampeding toward the newly sprayed land.
Like 1940's Melody Ranch, the 1941 Gene Autry vehicle Down Mexico Way was designed as a "special", to be promoted separately from Autry's regular B-western series as an A-picture attraction. The story gets under way when a pair of con artists, Gibson (Sidney Blackmer) and Allen (Joe Sawyer), breeze into the town of Sage City claiming to be movie producers. The two scoundrels promise to film a movie in the little burg on the condition that the townsfolk pony up the necessary production fees.
The Rough Riders are after a gang of rustlers. Marshal Roberts is posing as a wanted outlaw, McCall is the Marshal supposedly after him, and Sandy is on hand as a cook. Roberts hopes his joining the gang will help bring them in.
Rodeo champ Gene Autry inherits half interest in both a ranch and a mine that provides steady employment for the surrounding rancheros. Unfortunately, the other half goes to Easterner Barbara Erwin (Carol Hughes), who is only interested in monetary remuneration. To convince Gene to buy her share, Barbara enters into an unholy alliance with unscrupulous attorneys Arnold (Ivan Miller) and Fry (Sam Flint), who, without their client's consent, hire a gang of thugs headed by Tommick (John Merton). When a ranchero (Elias Gamboa) is mortally wounded in the ensuing gun battle, Barbara sees the error of her way and switches sides.
The Rough Riders are called in to help save Master's stage line. Taggart has his gang robbing the stages and shooting the drivers. When Buck drives the next stage, Taggart's men rob it and then make it look like Roberts is part of the gang. Written by Maurice Van Auken
The conflict between a railroader and a stage line owner is being aggravated by bad guys who are sabotaging both sides. Roy and Gabby mediate the conflict and expose the bad guys.
The notorious outlaw Black Bart has reappeared and the Range Busters are sent to investigate. When they find that Black Bart is now a respectable citizen and that someone is impersonating him, they set a trap for the robber.
The mayor has sent for a gunslinger who, though appearing to clean up the town, is really to be the mayor's means of taking the town over. When Roy and Gabby arrive in Tombstone, Roy is mistaken for the gunslinger. Just as Roy is ready to expose the mayor, the real gunslinger shows up.
Roy is a newspaper reporter. He goes to Cheyenne to cover the activities of supposed bad guy Arapahoe Brown. Roy, of course, discovers who the real bad guy is.
Gene returns from the East with new ranch owner Tom Bennett to find everyone's cattle dying. Blaine has reopened the copper mine and the waste is poisoning the water supply. While Gene is away Tom confronts the miners and a man is killed in the ensuing gunfight. Now Gene not only has the dying cattle problem but his ranch owner is in jail.