The rocketship MR-1 (for "Mars Rocket 1"), returns to Earth after the first manned flight to Mars. At first thought to have been lost in space, the rocket reappears but mission control cannot raise the crew by radio. The ground crew land the rocket successfully by remote control. Two survivors are found aboard: Dr. Iris Ryan (Naura Hayden) and Colonel Tom O'Bannion (Gerald Mohr), the latter's arm covered by a strange alien growth. The mission report is recounted by Dr. Ryan as she attempts to find a cure for Colonel O'Bannion's arm.
While exploring Mars, Ryan is attacked by a carnivorous plant, which is killed using a freeze ray (nicknamed "Cleo") fired by Chief Warrant Officer Sam Jacobs. They also discover an immense bat-rat-spider creature, after mistaking its legs for trees, and the monster is repelled, again by Jacobs. When they return to their ship, the crew find that their radio signals are being blocked and the MR-1 is grounded by a force field. O'Bannion leads the crew to a Martian lake with a city visible on the other side. They cross in an inflatable raft, only to be stopped by a giant amoeba-like creature with a single spinning eye. The creature kills Jacobs and infects O'Bannion's arm. The survivors escape to the MR-1 and commence liftoff. Professor Theodore Gettell, the ship's designer, dies of an apparent heart attack due to the stress of the lift-off from Mars. The survivors then return to Earth, where O'Bannion's infected arm is cured using electric shocks.
When the mission scientists attempt to examine the expedition's data recorders, all they find is a recorded message. An alien voice announces that the MR-1 crew were allowed to leave so they can deliver this message to Earth. The Martians have been watching human development throughout history, believe our technology has outpaced cultural advancement, and accuse mankind of invading their world. They warn humanity to never return to Mars or Earth will be destroyed in retaliation.
Melchior, the director, was given 10 days and a budget of $200,000 to make the film. The shortened production time necessitated the use of a CineMagic technique, which involved using hand-drawn animations together with live action footage, and it was used for all scenes on the surface of Mars. Although this process was largely unsuccessful, producer Norman Maurer would attempt the same technique again in The Three Stooges in Orbit.