Teenage photographer Peter Parker is sent by the Daily Bugle to investigate a series of mystery lights in a wooded area outside of the city, when a sudden landslide forces him to swerve off the road and land in a tree.

On a blistering hot afternoon, Peter is walking to the house of a brilliant scientist, Doctor Smartyr, when suddenly he notices that the sidewalk and most of the neighborhood is turning to ice. Hearing desperate cries for help from Smartyr's house, Peter changes into Spider-Man and breaks through a laboratory window to find the frightened scientist being menaced by a towering ice creature. It leaves, and Spider-Man finds a giant iceberg in New York Harbor. He returns to Dr. Smartyr, who deduces that the ice creature comes from Pluto; however, more ice creatures arrive, freezing him and Smartyr and kidnapping the scientist. The ice creatures actually do turn out to be 'Plutonians' and are not hostile. They are seeking out Dr. Smartyr for a way to help them get back to their home planet.

Peter flies to Florida to find and photograph the Lizard Man. Spider-Man meets Dr. Curtis Connor's family. He is pulled underwater by the Lizard Man, but escapes. In Dr. Connor's lab, Spider-Man finds out about the doctor's research on swamp fever and mixes an antidote for reptilian mutation. He fights the Lizard Man in a ruined Spanish fort and turns him back into Dr. Connor.

Spider-Man is set up numerous times by Electro's robberies. Electro first robs J. Jonah Jameson's house and escapes before the police see him, though they see Spider-Man. Peter shows Jameson the photo, but he throws it away. Spider-Man finally tracks Electro to an abandoned amusement park and catches him using a new web. He leaves him hanging outside of Jameson's window.

Spider-Man has been witnessed committing a robbery of the Midtown Museum. Mysterio phones J. Jonah Jameson and makes a deal to defeat and expose Spider-Man in exchange for a large sum of cash. He fights Spider-Man on a bridge. Spider-Man is unable to beat him and dives from the bridge to escape. He finally tracks Mysterio to a film set and records Mysterio's confession that he robbed the museum disguised as Spider-Man. He then beats Mysterio.

The Vulture uses a sonic device in his head mask to control an army of vultures. After the Vulture beats Spider-Man, he holds the city for a $2,000,000 ransom and J. Jonah Jameson blames Spider-Man. Spider-Man takes the ransom to the Vulture and uses this opportunity to sabotage the Vulture's device so the vultures attack him, then returns the ransom.

While Spider-Man is out he is almost caught by a robot. Later an inventor named Henry Smythe reveals his plans to capture Spider-Man with the robot and get paid by J. Jonah Jameson for his efforts. Although skeptical at first, Jameson becomes enthusiastic when the robot is activated and starts zeroing in on its target. Peter makes a hasty retreat from the editor's office, but the robot lumbers after him into the street. Ducking into an alley, the teenager changes to Spider-Man before leading the robot on a frantic chase throughout the city. When the robot catches him Betty enables Spider-Man to escape by pulling out the plug to the controls; however, Jameson sends her out. Spider-Man is finally caught again by the robot after knocking himself unconscious by swinging into a clock tower. However, he breaks into the robot's interior circuits and is able to free himself from the robot's tendrils.

Dr. Stillwell creates the Scorpion on J. Jonah Jameson's behalf to capture Spider-Man. The Scorpion attacks Spider-Man, who escapes. However, the Scorpion's evil nature takes over as his strength increases which causes him to go after Jameson, but Spider-Man captures him and the Scorpion is arrested. However, he breaks out of prison and goes after Jameson again while Spider-Man is searching for him, but Spider-Man arrives in time to fight the Scorpion, who is webbed up and imprisoned again.

As Spider-Man examines the Goliath Diamond, the Sandman appears and swipes the diamond, with Spider-Man getting the blame as he is seen by the guards. The Sandman demands a $1,000,000 dollar ransom from J. Jonah Jameson. Spider-Man fights him where the ransom is due to be delivered, but the Sandman escapes before Jameson arrives and takes the ransom, only to find that he has been given a rock. Finding out that Jameson has given him a suitcase filled with pieces of paper, the Sandman demands $2,000,000. Spider-Man fights him at a rock quarry and defeats the Sandman by knocking into a trough of water, making him soggy. He then squirts the Sandman with more water from a hose, weakening him and forcing him to surrender the diamond, finally leaving him for the police. However, Peter forgot to take any pictures.

Spider-Man witnesses, and photographs, a giant metal-eating robot in Central Park. It is never explained who built it. The robot sets the park on fire and while Spider-Man stops the fire spreading, it leaves. Spider-Man fights the robot throughout the city and finally causes it to fall into the river.

Electro escapes prison before Spider-Man can stop him using a metal kite during an electrical storm to renew his powers. He takes the electricity supply of the city, demanding a ransom from the city. Spider-Man tries to stop him at the factory, but only just escapes being drawn into a generator. However, Spider-Man is able to catch Electro by trapping him in an electric spider web.

Spider-Man faces off against Parafino, a wax museum owner who plans to make Spider-Man into his latest exhibit. He uses escaped convict Red Dog Melvin as bait for Spider-Man, disguising him as a waxwork. He catches Spider-Man using a wax sculpture of himself and captures Betty Brant when she comes to the museum. However, Spider-Man frees himself and destroys the wax Parafino by increasing the heat. While Betty gets the police, Melvin revives and attacks the real Parafino. Spider-Man webs them both up.

Spider-Man is keeping an eye on a train when the Rhino rams into it and steals the first component of a top secret weapon, with Spider-Man getting the blame. Meanwhile, Peter has a cold, and his Aunt May wants him to stay in bed. The Rhino then steals another component from an airport. At May's suggestion, J. Jonah Jameson decides to take his own photos. However, when he tries to enter a military area wearing a disguise, he is stopped by a guard. He complains about this; however, his disguise falls of and he is arrested. The Rhino steals the final component from a submarine. The police put a dragnet out but cannot find the Rhino. Spider-Man finds him hiding in a cave with its entrance in the pool of the rhino exhibit at the zoo and catches him using pepper.

Someone has sent a one-eyed idol to J. Jonah Jameson. Jameson is hypnotized by the idol to steal his own money. Spider-Man finds the thief, but he escapes with the money. The next day Jameson is again hypnotized to steal more money. Spider-Man attacks the thief, but is knocked out by a boomerang, and finds the mastermind is the hunter Harley Clivendon, who tries to kill Spider-Man using an elevator. However, Spider-Man frees himself and captures both crooks.

Spider-Man attempts to halt the Phantom's activities only to be set up by him and his robot henchwoman Marie, who is disguised as a shop window mannequin. He discovers the Phantom is using shrinking rays to steal items. However, some of the shrunken items are in a dollhouse in the Daily Bugle. The Phantom gets into the Bugle's offices and escapes with the dollhouse. Spider-Man is finally taken to the Phantom's base and defeats both him and his three robot henchwomen.

Spider-Man saves a boat from Dr. Matto Magneto's attempt to crash it on the rocks by sabotaging a lighthouse. Determined to prove his magnetic power, Dr. Magneto sabotages a railway line, which Spider-Man fixes. Magneto next tries to make the statue of Prometheus fall off of the top of the Empire State Building, but Spider-Man catches it in his web. Dr. Magneto meets Spider-Man at the Hall of Fame and captures him, planning to lift the entire Hall into the air by magnetism and drop it into the ocean with him in it. However, Dr. Magneto is beaten with Spider-Man's anti-magnetic webbing that destroys his weapon.

Spider-Man gets into an embassy, and sees the foreign visiting Prime Minister tied up and gagged, and fights someone impersonating the Prime Minister, but he is forced to retreat to find proof after being gassed by the imposter's cane and having his camera stolen. The imposter convinces Jameson to help raise money for his nation, and gets $20,000,000. Spider-Man gets into the embassy again and defeats the Imposter, but is forced out. The imposter tries to leave with the gold via airplane, but Spider-Man catches him, exposes him as Charles Cameo before the police, and frees the real Prime Minister.

Historic villains Blackbeard the Pirate, Jesse James, and the Executioner of Paris are committing robberies in New York City, and Spidey tracks them to their lair- Parafino's Wax Museum, where Spidey's wax-master enemy is scheming to besiege and plunder the city with robotized wax villains.

Miss Trubble, a book dealer obsessed with mythology, is owner of a magical chest from which she summons a succession of mythological figures, from centaurs to the Cyclops to Diana the Hunter-Goddess, to commit robberies of ancient artifacts on her behalf.

A scientist, Dr. Noah Boddy, renders himself invisible by means of a machine, then acts to avenge himself upon Jameson, who publically maligned his theory of invisibility.

Spiderman battles an Arabian jewel thief, whose magical flute induces animals into attacking Spidey.

Reports of a legendary, flying ghost ship, the Flying Dutchman, being sighted near Smuggler's Cove summon Spidey to the area, where his investigation into the phantom ship's appearance leads him to a cave in which he finds his sworn adversary, Mysterio, plotting with a pair of thugs.

When a Jekyll-and-Hyde poster comes to life at the soon-to-be-demolished Castle Theatre, Spidey visits the theatre and encounters a mischievous Blackwell the Magician, who is trying to attract public attention to the theatre in hope of preventing its demolition.

Spiderman's old enemy, the rampaging Rhino, is stealing gold bullion to mold an auric likeness of himself.

A bald-headed mastermind named the Plotter employs two ridiculous criminals, Cowboy and Ox, to steal a blueprint to a missile.

Spidey chases the culprit in an attempted theft of jewels from a countess and is surprised to find that his opponent, dressed in a black ""Human Fly"" costume, also has the ability to scale walls and can cross thin wires between buildings.

Oil is being stolen in huge quantities by Dr. Von Schlick, a chemist villain garbed in a rubber, non-stick suit and armed with petroleum-based bubbles that he fires from his fingers to envelope Spidey.

The nefarious Vulture traps Jameson inside of a tower-clock and uses the well-informed Daily Bugle publisher as a source of information on the whereabouts of a visiting diamond merchant and the testing of military equipment- two prospective heists for the greedy bird-man.

Life-like and substantial shadows of beasts are projected in various locations in New York City by the Phantom's new Shadow-Scope glasses to cause panic and enable the Phantom to effect unconstrained bank and jewelry store robberies.

Doctor Octopus imposes upon Dr. Smartyr's Nullifier rocket test and steals the ultra-powerful destructor missile, with possession thereof Octopus plans to force all nations to bow to his will.

While Blackwell the Magician is entertaining at the Castle Theatre, his house is invaded by the Green Goblin, who swipes some of Blackwell's props and peruses Blackwell's book of magic spells and incantations.

Dr. Curtis Conner goes missing in the Florida swamps after finding the Fountain of Youth. When Spidey investigates the scientist's disappearance, he discovers a fifteenth century Spanish conquistador, Ponce de Leon, who is intent upon keeping the magical fountain a secret.

Because he hates rock-and-roll for its having replaced classical music in the tastes of the masses, a fiddler with a deadly, sonic violin seeks revenge upon pop-music sponsor Cyrus Flintridge.

Under the guidance of Dr. Noah Boddy, the Green Goblin, Electro, and the Vulture join forces for revenge on Spiderman. In a confrontation with Noah Boddy's three stooges, Spidey practices ventriloquism to cause each of the three miscreants to think that he is being insulted by the others, and the excitable trio of villains begin fighting each other.

Art robberies are committed by an old enemy of Spiderman, actor Charles Cameo, who can utilize masks and make-up to usurp any identity, including those of J. Jonah Jameson and Spiderman!

When the Scorpion, intent on vengeance upon Spiderman and Jameson, escapes prison, he visits the laboratory of his creator, Dr. Stillwell, and drinks a potion that vastly increases his size.

Paroled from prison, the Human Fly Twins rob diamonds from an importing company, and one of them does this deed in a Spiderman costume so that the guard, before being hit on the head from behind by the second twin, believes that Spidey is the culprit.