Gags include a glass of water rigged to explode when lifted, Wile E. chasing on fast-powered skates, and building a fake railroad.
- Introduction: The Road Runner flips the title cards by passing across. The chase begins as normal, and is then paused for the Road Runner (Accelerati Incredibilus). The camera zooms back to the Coyote (Carnivorous Vulgaris). The camera then zooms back to the Road Runner and the chase resumes. The camera now zooms out as Wile E. chases after the Road Runner with a knife and fork. The Coyote strikes - and misses, sticking the utensils into the road as the Road Runner moves into super speed. Wile E, left suspended in the road, lets go of the knife and scratches his head, only to fall down. He slumps on the ground and soon comes up with a new plan.
- The Coyote attaches a spring-activated boxing glove to a large rock and hides behind it, hoping to strike the Road Runner. However, the tension in the spring causes the rock and Wile E. to be launched backwards instead of the glove forwards. The glove then retracts backwards and punches the stunned Coyote in the face.
- Wile E.'s next plan is to traverse a tightwire and drop an anvil on the Road Runner, resulting in a "Road Runner Burger" as his drawing puts it. Obviously, the anvil is too heavy for the tightwire to handle, and Wile E. is stretched all the way to the ground and can be seen by the Road Runner, who taunts him before dashing off. Wile E. drops the anvil and is thus slung up into the air. Eventually, he peaks and falls downwards. Wile E. points expectantly at his backpack and pulls out a cord, hoping for a parachute; however, upon opening the pack, there is no parachute, simply common items like a hatchet and kitchen utensils. Wile E.'s expression darkens as he knows what will happen now, and he then pulls out a pack of Acme Aspirin to alleviate the inevitable pain. He weakly waves at the camera as he takes the plunge (see "Censorship")
- The Coyote then tries a new plan to explode the Road Runner with trickery: set out a water glass with two signs by it reading "Last Water for 300 MILES" and "Free Drink of Water". Of course, nothing provided by Wile E. Coyote is free. It comes with "strings attached", that is, a string to a TNT device, which, as he hopes, should eliminate the Road Runner. Wile E. hides as he hears the approaching Road Runner, who stops at the water stand, mockingly spits at it, and speeds behind the hiding Coyote with a tall, large sign that reads "ROAD RUNNERS CAN'T READ AND DON'T DRINK". The Coyote's expression turns from smug to incredulous to outraged in a matter of seconds. He chases the Road Runner into an Old Cactus Mine, but soon realizes he has no helmet or flashlight. He returns to the cap rack and dons a cap, and the Road Runner pulls up to him and provokes a chase through the mine. They chase in a straight line until the Road Runner loads himself into an elevator and speeds to safety. For this section of scene three, the camera cuts alternately to an actual-size view inside the mine and a Pac-Man style view. Their hats color-code the characters during the latter period: the Road Runner is green and the coyote is red.
- Real time: Wile E. brakes before falling into the shaft and gets into another lift to the left.
- Pac-Man: The Coyote's lift descends until he spots the Road Runner in another shaft to the right, and follows him through it. The Road Runner ascends a level, flies over a gap, and causes the Wile E. to pause, then to jump and hold onto...
- Real time:...the edge of this tunnel, and then to disappear through that tunnel.
- Pac-Man: The Road Runner continues running down a level and then back up the same way he came.
- Real time: Wile E. is momentarily stalled by having to climb a ladder up the main shaft.
- Pac-Man: The chase continues circling in this way and gets faster and faster until the Road Runner edges into the right shaft. Wile E. continues circling at ever-quicker speeds until the Road Runner beeps at him, which alerts him to continue the chase. Past this shaft is an up-and-down zigzag shaft; Wile E. and Road Runner follow this until the shaft changes into a straight tunnel to the right and one to the northeast. The Road Runner moves into the northeast tunnel, while Wile E. continues moving in the same pattern, bumping himself many times upon the ceiling and floor of the east shaft. Eventually, he knocks out his headlight.
- Real time: Wile E. lights a match for light, but happens to be in an explosive-laden tunnel. The camera then cuts to above the surface. The explosion warps the cacti currently on camera into the word "YIPE!".
- Back on the surface, Wile E. has loaded himself on a springboard in order to sling himself towards the passing Road Runner. When he cuts the rope holding him back, he is planted directly on the ground and the spring unfurls like a Slinky.
- The Coyote is now waiting for the Road Runner to make a turn so that he can chase him with an abstrusely designed rocket. He lights the fuse with perfect timing, but unfortunately, the rocket fires directly up into the sky and explodes into an EAT AT JOE'S sign.
- Now, Wile E. uses ACME's rocket-powered roller skates to prepare for the chase, which the Road Runner promptly begins by pulling up to the Coyote. The rocket thrust almost unseats the Coyote, but he manages to lift his midsection to normal height and begin a very promising chase. When the road takes a turn, however, the Coyote is catapulted off the end, his rear is bumped against the tops of several buttes, and he is then plopped on top of a high plateau. The skates are still functioning, and the jet blasts eventually join forces and continue to rush the Coyote forward. Wile E. is then thrown up into the sky, where the skates tucker out. The Coyote, knowing about the adverse effects of gravity on him, begins to pray then pulls out a wreath with R.I.P. on it as he falls into the ground. Wile E. climbs out of the hole he makes exhausted, and soon spots his "Free Drink of Water" trap set earlier in the cartoon. As he is thirsty, he lifts the glass and gets blown up.
- The fully recovered Coyote places a small railroad track, two bushes, himself, and a "R.R. STOP" sign in the middle of the road. This fails to stop the Road Runner, who mows down the Coyote and leaves him spread-eagled on the track to be flattened again by a train passing through additional tracks mysteriously set up. The Road Runner relaxes on the balcony of the caboose, with a "THE END" sign attached to the back of the caboose.
- VHS - Road Runner and Wile E. Coyote: The Classic Chase
- LaserDisc - ROAD RUNNER VS. WILE E. COYOTE: If At First You Don't Succeed...
- DVD - Looney Tunes Golden Collection: Volume 2, Disc Two
- Blu-Ray, DVD - Looney Tunes Platinum Collection: Volume 1, Disc 1
When this cartoon aired on Nickelodeon, the scene of Wile E. Coyote finding out his parachute is actually a knapsack filled with camping gear as he falls was edited to remove him taking out a pack of Acme Aspirin and swallowing them before waving pathetically at the camera and falling to the bottom of the gorge.
- Gag #5 was used in the Thanksgiving special, Bugs Bunny's Thanksgiving Diet.
- Space Jam shows Coyote's second attempt from this short, shown when Michael Jordan's children watch TV. However, Porky Pig shows up to remind Coyote and Road Runner about a union meeting (where the aliens decide to take them to Moron Mountain). Road Runner then runs off with Porky telling him to wait while Coyote tries to follow them but is sent flying from the tightwire like a slingshot and then crash lands in Union Hall 839.
- According to Michael Barrier on the audio commentary for Fast and Furry-ous, the cartoon was originally going to be called "The Pursuit of Slap Happiness".