The 1933 version of the work of H.G. Wells opens with title and credits. A man trudges through the snow to the small village of Iping. His destination is the Lion's Head Pub and Inn. The place is a buzz of activity: drinking and laughing, and a game of darts. The stranger, Dr. Jack Griffin (Claude Rains) walks in covered from head to toe, head bandaged, and wearing a false nose. All sound in the Pub ceases. The stranger approaches the proprietor, Herbert Hall (Forrester Harvey) and requests, "I want a room and a fire." Hall calls to his wife, Jenny (Una OConnor). Jenny explains they have no rooms ready, as summer is their normal season, but one can be prepared. Jenny calls to Minnie (Merle Tottenham). Jenny leads Dr. Griffin to his room, sending Minnie on ahead. Minnie lights a lamp while Jenny builds a fire and explains, "It's the coldest winter we've had down here for years." Griffin asks about his luggage, but Jenny explains she'll arrange for it in the morning. His final request before Jenny departs is for some food. Griffin closes the drapes in his room.
The townsfolk are suspicious of the stranger. One man speculates, "If you ask me, he's a criminal flying from justice." He advises Herbert to lockup his money. Jenny carries a tray up to his room and walks in without knocking. Griffin asks about a key and is told there is none. He emphatically states, "I want to be left alone and undisturbed." Jenny leaves and Griffin removes his coat. Jenny returns to the kitchen only to be told by Minnie that she forgot the mustard. Jenny makes a second trip to Griffin's room. Again she does not knock, just bursts in. Griffin is seated, and the lower half of his face is gone. Jenny is shocked by what she sees as Griffin masks his face with a napkin. Griffin angrily reminds the landlady, "I told you not to disturb me." Jenny cautiously approaches, mustard in hand, and asks Griffin if he's had a motor car accident. Griffin tells Jenny to take the overcoat to dry, but leave the hat. Jenny leaves Griffin's room. She runs downstairs to report to all who'll listen, "Bandages right up to the top of his head, all around his ears."
At a large country home, Dr. Cranley (Henry Travers) works in a large room converted into a laboratory. His daughter, Flora Cranley (Gloria Stuart) enters the lab wishing to speak. Dr. Cranley admonishes her, "I wish you'd leave me alone, Flora, when I'm working." Flora is concerned nothing is being done about Jack. He has been away for a month now and no word from him. Dr. Arthur Kemp (William Harrigan) enters the room and is told Flora is worried about Dr. Jack Griffin. Flora storms off sobbing, and Arthur tries to comfort her. Dr. Kemp tells Flora, "He meddled in things men should leave alone." The group was working on food preservation advances, but Jack preferred to work in secret. Flora is interested in Jack romantically, as is Dr. Kemp.
A week later, Griffin is in his room. He has set the place up as a mini-laboratory and mutters to himself, "There's a way back, you fool. There must be a way back." Jenny arrives with Griffin's lunch, but he still doesn't want to be disturbed. He slams the door closed and she drops the tray. Jenny tells her husband she wants him out, his room is a mess and he is behind on his rent. She sends her husband to do the dirty work. The disturbance annoys Griffin, "And a whole days work ruined...by a foolish, ignorant woman!" Hall barges his way into Griffin's room with bill in hand. Griffin explains his money will be forthcoming. He explains he is working and pleads for a little more time, undisturbed. Griffin admits he had an accident that disfigured him and it affected his eyes. Hall won't budge, so Griffin turns hostile. He tosses Hall out of his room and down the stairs. Bruised and bleeding, Hall comes to in the arms of his hysterical, shrieking wife. The police are summoned.
Constable Jaffers (E.E. Clive) is surrounded by the townsfolk. He asks what's all this and is told the stranger with the goggles has gone mad, assaulted Mrs. Hall and nearly killed Mr. Hall. Jaffers pulls out his baton and walks upstairs, followed closely by half a dozen men. Jaffers confronts Griffin. He intends to arrest Griffin, but Griffin threatens, "All right you fools. You've brought it on yourselves...now you'll suffer for it! You're crazy to know who I am, aren't you? All right, I'll show you." Griffin proceeds to remove his false nose, and then his goggles. The head under the bandages is hollow. Next he removes the bandages, laughing maniacally. Jaffers observes, "Look. He's all eaten away." They all run from Griffin's room. Jaffers and a few men return to his room, but all that is visible is a shirt bobbing in the air. Griffin explains that all that was needed is a few chemicals mixed together, "Flesh and blood and bone just fade away." Jaffers closes the door, but Griffin takes the window to exit the room. Jaffers runs to the window, but to his surprise, Griffin taunts him, "Think I'd escape like a common criminal? You need a lesson. I think Ill throttle you." Griffin beats up the men guarding the door, then escapes downstairs knocking the grandfather clock over in the process. He steals a bicycle and rides off, and then menaces the townsfolk with pranks.
Doctors Cranley and Kemp go through the fireplace ash looking for clues to Griffin's work or location. They did find a list of drugs and chemicals. The last on the list is monocaine. Cranley explains that monocaine is a terrible drug: made from a flower grown in India. It draws color from everything it touches. It was tried as a bleach for cloth, but destroyed the material. In a German experiment it was used on a dog: it bleached it white and drove it mad.
Griffin enters the home of Dr. Kemp. He opens the French door and a gust of wind is blamed for a paper flying off his desk. A radio broadcast reports a mass delusion among the people of Iping; they believe an invisible man is living among them. Kemp makes the connection just as Griffin shuts off the radio and announces his presence, "And everyone deserves the fate that's coming to them: panic, death, things worse than death. Don't be afraid Kemp. It's me, Griffin." A rocking chair moves across the room and the seat collapses downward. Kemp is shocked. Griffin threatens Kemp. He tells him to sit down and listen to his story. After insulting Kemp, Griffin demands a surgical bandage, a pair of dark glasses, a dressing gown, pajamas, and a pair of gloves. Griffin go to a bedroom to put his pajamas on. He continuously threatens Dr. Kemp.
Chief Detective (Dudley Digges) arrives at the Lion's Head. He is annoyed and doesn't believe the stories after a ten mile search of the area. He thinks it is a hoax being used to generate publicity and business for the Pub. The inspector starts an inquiry. Back at Kemp's home, Griffin exits the bedroom covered from head to toe. Griffin and Kemp sit and talk in the study. He tells Kemp it started five years earlier, working in secret: a thousand experiments and a thousand failures. He admits he was working on an antidote. Then Griffin admitted, "It came to me suddenly. The drugs I took seemed to light up my brain. Suddenly I realized the power I held. The power to rule, to make the world grovel at my feet. Well soon put the world right now, Kemp. You and I." Griffin needs a visible partner. He adds, "We'll begin with a reign of terror, a few murders here and there...We might even wreck a train or two." Kemp admonishes his colleague, but is cowed by the threats. Kemp gets his car, as instructed, and they drive back to Iping to get Griffin's notes.
The detective questions the townsfolk, including the bicycle owner (an uncredited Walter Brennan). Kemp and Griffin stop a short distance from the Pub. They walk to the Pub. Griffin enters the Pub and walks upstairs to his room. He gathers his books and notes and passes them through the window. As the detective goes to sign some papers the ink well moves around on the table by itself. The ink is thrown on the man's face. Mugs and pitchers fly off the walls and counters at the assembled police and witnesses. They all run from the Pub. Griffin chokes the Chief Detective and hits him with a stool. Griffin runs back to the waiting car. Dr. Cranley goes to see Inspector Lane. A crowd gathers around a newspaper boy distributing the latest news on the Invisible Man. The newspaper headline blares, "Invisible Man Slays Policeman."
Griffin reveals to Kemp he must remain in hiding after meals. The food is visible inside me until it is digested. I can only work on fine, clear days. If I work in the rain, the water can be seen on my head and shoulders. In a fog, you can see me, like a bubble. In smoky cities, the soot settles on me until you can see a dark outline. Griffin goes to bed after taking off his head bandages and dark glasses.
The Chief of Police (Holmes Herbert) gives orders to his men on the plan to search the countryside for twenty miles in all directions. A contingent of a thousand men, and thousands more volunteers will comb the countryside. At 10:30 p.m. a radio broadcast explains that the story is not a hoax and volunteers are needed. A reward of 1000 pounds is offered. Kemp checks on Griffin to make sure he is asleep. He calls Dr. Cranley to tell him Griffin is mad and is the Invisible Man. Cranley tells his colleague he will come in the morning, but for the time being, keep Griffin calm and quiet. Flora demands to know the truth and her father tells her. A man (an uncredited John Carradine) suggest throwing ink on the Invisible Man to make him visible. Dr. Kemp calls the police and reports that the Invisible Man is asleep in his home. Flora wants to help, but her father explains it is dangerous, as Griffin is mad and dangerous. Dr. Cranley and Flora drive over to Kemp's house. Kemp admits he told Cranley when Griffin accuses him of betrayal. Despite warning, Flora goes to see Griffin in his room. Griffin tells Flora he did it all for her, to gain wealth and fame and honor. He intends to sell the secret of invisibility to the highest bidder to allow invisible armies to sweep the world. Griffin rants and raves. Flora explains that monocaine has a terrible side effect. The police surround the Kemp home. Griffin escorts Flora out of his room so he can deal with the police. The police link arms and move towards the house. Griffin confronts Kemp in his office. He promises his friend to kill him the next day at 10:00 p.m. Griffin taunts the police and escapes.
The Chief of Police questions Cranley and Kemp, but gets little information. Griffin attacks a search party. He derails a train, sending it crashing into a river killing one hundred people. At Lloyd's Bank he steals a cashiers drawer and hands out cash to eager people on the street. A reporter (an uncredited Dwight Frye) asks the Chief, "Can you tell us what plans you've got for capturing him?" At the Cranley home, Flora paces her room. After sweeping an empty room with a net, the Chief divulges his plan. It involves the death threat on Dr. Kemp. Kemp objects to being used as bait. The plan also includes dressing Kemp up like policeman. Kemp decides to see to his own safety. He drives his own car away, but Griffin is in the back seat. Griffin gloats, telling Kemp the story of watching the elaborate plan for his safety. Griffin ties up Kemp, places him back in the car and pushes the vehicle over a cliff. The car explodes into flames.
Griffin sleeps in a barn overnight. The farmer sees the hay move and walks over to investigate. It begins to snow. The farmer walks into the police station to report the Invisible Man is in his barn. The plan now is to burn down the barn and follow the footprints in the snow should he escape. The Chief fires on the Invisible Man, using his footprints in the snow to take aim at his target.
At hospital, a doctor reports to the Chief that, "He's very near the end." The doctor explains to Dr. Cranley that the bullet passed through both lungs. The wounds are impossible to treat. As he dies his body will become visible. Flora goes into his room to be with Griffin. We close with a close-up view of a hospital bed and pillow. At first a skull appears resting on the pillow, then his eyes, and finally the face of Dr. Jack Griffin.