Bad guys plot to trick a newly arrived Eastern girl out of a ranch which belongs to her infant ward. Roy, of course, saves the ranch for the girl. Songs include "I'm Headin's for the Home Corral," "He's a No Good Son of a Gun," "Sandman Lullaby," "Song of the San Joaquin," and "I'm a Cowboy Rockefeller."
Radio star Gene Autry returns to his home town of Gold Ridge at the request of his old friend Pop Harrison, who wants Gene to straighten out his wayward son, Tex Harrison, whose gambling and drinking threaten to bankrupt the rodeo organization which he heads. News photographer Clementine "Clem" Benson and reporter Hack Hackett are ordered to follow Gene. The group finds quarters at the "Bar Nothing" dude ranch, winter quarters for Tex's rodeo group, and Tex soon tangles with Hackett in a quarrel.
Judge Kirby is being blackmailed and forced to let outlaws go free. He was once the partner of Roy's father and when Roy reads in the paper that he is in trouble he heads out to help him. Arriving, Roy quickly realizes he has been mistaken for one of the outlaws and is not wanted in town. However he stays, and now posing as that outlaw, hopes to learn who is causing all the problems.
As foreman of a dude ranch, Gene has two problems. One is a guest, the spoiled daughter of a millioniare, and the other is the disgruntled ex-foreman that Gene replaced, now just a ranch hand. Gene eventually gets the daughter straightened out but has to fire the ex-foreman and this leads to trouble when he returns intent on revenge.
In Old Wyoming, a gang is plundering stagecoaches of shipped currency and a crusading newspaper editor is trying to get the local marshal replaced, because of his apparent failure to catch the gang, which seems to disappear into thin air after every robbery. The situation escalates when one of the stage drivers is mortally wounded; so the marshal sends for his friends, the Range Busters, to help him catch the criminals. Meanwhile, even the marshal's fiancee, the editor's daughter, turns against him in favor of an aggressive agitator for law and order - who secretly is leading the robber gang.
Stanton breaks Billy and his two friends Fuzzy and Jeff out of jail. He wants them free so three of his men can impersonate them for the robberies and murders he has planned.
To get the three needed business men to visit the Stevens mine, Roy stages a ride with the Vacaros and has them as honored guests. Seeing a chance to make a lot of money, gangster Harmon joins the ride and then has his men kidnap the three. Having filmed a fake holdup earlier, he uses the film to convince the Sheriff that Roy and the boys were the Kidnapers.
Gene Autry heads a cattlemen's association and calls on the inexperienced Jim Agnew to negotiate the sale of five hundred heads of cattle. Jim ends up losing the cattle in a crooked poker game, however, and Gene and his sidekick Frog set out to find the cheating gamblers. It soon becomes clear that the leader of the gamblers is none other than Asa Lock, the dastardly father of Gene's romantic interest Stephanie.
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.
Hoppy is leading a scientific expedition and the Chinese who have a hidden settlement nearby are trying to stop them. Saulters and his outlaw gang are also in the area looking for a gold mine. When Saulters men attack, the gold mine is found. Hoppy agrees to file for the Chinese and heads after Saulters in the chase to the land office.
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.