A famished Wile E. Coyote (Eatibus Anythingus) trudges across the desert floor, catching and eating anything that he finds to satisfy himself, ranging from a fly to - finding nothing inside - an entire tin can, before being flattened by the Road Runner (Hot-roddicus Supersonicus). Wile E., after recovering, blinks his eyes and visualizes a wonderful Road Runner feast. Seeing no need for a comparatively tawdry can, he chases the Road Runner.
Wile E.'s low stance reduces his drag and allows him to pull up near the Road Runner until the bird rockets away. The Coyote's eyes pop out of his sockets and he is left dejected, planning his next scheme.
First, the Coyote uses a pulley, rope and rock trap to smash the passing Road Runner, evidently hoping the extra complexity will stop himself from being squashed instead. No dice; Wile E. is sqished by his own trap as the Road Runner stops and makes fun of him.
Now, clearly angry, the Coyote holds a lasso out in the road and listens for the Road Runner, but instead of the bird, he gets a truck which pulls the lasso and the Coyote with it across the hard ground. Wile E. is left with a bare rear end from the friction as he paces off the road.
Wile E. builds a Burmese tiger trap according to an ACME How-To book: dig a square hole and cover it with a camouflaged sheet. The Coyote hides behind a rock and, hearing the Road Runner and the trap activating, dives in to capture his prey...but instead, he gets throttled by a real Burmese tiger (Surprisibus! Surprisibus!), which stealthily climbs out of the trap.
Wile E. has now constructed a massive pop-up grate in the middle of the road, and tests its crank control. But when it is meant to block the Road Runner, it fails to work. The Coyote tries every method possible to get the grate to function, but this fails. He resumes the chase in outrage, but not for long, as he gets stopped by a railroad crossing. The Road Runner taunts the Coyote as he slowly prances the tracks and his opponent is lifted into the air by the striped divider. Wile E. drops off and chases the Road Runner down the tracks, which run through mountains.
The two pass by opposite lanes and the Road Runner signals the Coyote, who stops cold after a few seconds and turns back...but too far again. He starts back the other way and soon finds the Road Runner is on a lower track than he is. They finally chase on the same track until a train stops the chase. The Coyote dashes in and out of a rockface and sees the train pass by on a track underneath him. He sighs with relief - until a second train approaches where he is standing from inside the rock. Wile E. holds up a circular STOP IN THE NAME OF HUMANITY sign, but since Wile E. isn't human, nothing happens except for the massive impact.
Next, Wile E. moves into a grooved pipe intending to set TNT underneath the road, but the detonator hangs up on a loose rock and blows the Coyote up while he's still inside the cave.
The Coyote now has possession of an insanely fast motorcycle, but when he starts it to chase a passing Road Runner, he simply slams into a tree and is jiggled around by the intense engine vibrations.
Now, Wile E. has painted a white circle in the middle of a large suspension bridge and baits it with bird seed, then hides underneath the bridge to cut out the circle as the Road Runner feasts. Instead, he cuts out the rest of the bridge with him underneath it, leaving the Road Runner and the circle floating in midair.
Finally, the Coyote attempts to outrun his rival by taking ACME Triple-Strength Fortified Leg Muscle Vitamins. He burns rubber on the road, then dashes off fast enough to leave the highway on fire. This warp-speed chase continues until they pass by the cranked-up grate, which finally decides to raise itself in between the sprinters. Wile E. smashes into the grate, and the Road Runner brakes and views his hapless rival before burning more rubber on the road, spelling out "That's all, folks" in smoke.