This is a comprehensive list of the differences between the film and the book.

Book Film
Percy Jackson only goes to Camp Half-Blood during the summer. Percy is a year-rounder at Camp Half-Blood, meaning he lives there all of the year.
Tyson and Percy are friends at Meriwether College Prep. Tyson and Percy meet for the first time at camp.
The Great Prophecy is not revealed to Percy until The Last Olympian. The Oracle of Delphi tells Percy the prophecy.
The Great Prophecy is on a piece of paper in a necklace that the Oracle wears around her neck. The Oracle tells Percy the prophecy.
Clarisse goes to see the Oracle to receive a prophecy for her quest. Percy visits the Oracle for the first time and learns of the Great Prophecy.
The Great Prophecy comes true at age 16. The Great Prophecy comes true at age 20.
While searching for Pan, Grover Underwood gets lured by Polyphemus and becomes trapped there. Grover is captured by Luke Castellan and sent to Polyphemus.
Three Hippocampi pick up Percy, Annabeth Chase, and Tyson in order to take them to the Princess Andromeda. One giant Hippocampus takes the trio to Luke's yacht.
Mr. D drinks Diet Coke. Whenever Mr. D pours wine into a glass it turns into water.
The Princess Andromeda is a large cruise ship that Luke uses to house the many monsters and demigods in the Titan Army. Luke's ship is a small yacht with a limited number of monsters and demigods.
Ethan Nakamura debuts in The Battle of the Labyrinth. Ethan appears on Luke's ship.
Silena Beauregard is a spy and is not revealed to be a spy until The Last Olympian. Silena appears on Luke's ship.
Hermes appears to Percy on the beach at Camp Half-Blood and gives him some gifts to help on his quest. Annabeth, Tyson, and Percy go to meet Hermes at the Olympic Postal Service, which is disguised as a UPS store.
Hermes gives Percy the Thermos of Winds and a container of multivitamins. Hermes gives them the Thermos of Winds and a magical tape that makes things disappear.
Annabeth calls on the Gray Sisters' Taxi in New York in order to take them to Camp Half-Blood. The Gray Sisters take them from Camp Half-Blood to Washington DC.
Percy and Annabeth are separated from Clarisse and Tyson when Charybdis causes the CSS Birmingham to be pushed into Scylla, eventually causing the ship to explode. Clarisse, Percy, Annabeth, and Tyson are all swallowed by Charybdis, but eventually escape. Scylla is only referenced, but never seen.
Like most cyclopes, Tyson can breath underwater as he is a child of Poseidon. Water can heal Tyson, much like how it does for Percy.
Kronos does not rise and take a host until The Battle of the Labyrinth. Kronos rises without a host.
Chiron is sent away and replaced by Tantalus. Chiron is present. Tantalus is never shown.
Annabeth and Percy get stuck on Circe's Island, where Circe and her handmaidens appear as one of the many challenges Percy and Annabeth face in the Sea of Monsters. The trio go to Circe Land, which is an abandoned amusement park. It is also Polyphemus' hide out.
Polyphemus has his own island. Polyphemus' hide out is at Circe Land.
Percy asks his dad for a ride to Luke's ship and is sent three hippocampi. Tyson asks his dad to send a ride, which he does in the form of one large hippocampus.
Tantalus picks Clarisse La Rue to go on a quest to find the Golden fleece. Mr. D selects Clarisse to go on the quest.
Clarisse has been going to camp for years, even before the arrival Percy Jackson. Clarisse is a newer camper.
Clarisse and Percy have a rivalry because of Percy defeating Ares and because he defeated Clarisse in Capture the Flag (as well as spraying her with toilet-water). Clarisse and Percy are simply rivals, both competing to be the best at camp.
Tyson supposedly sacrifices himself to save Percy when the CSS Birmingham blows up. Tyson supposedly sacrifices himself to save Percy from being shot with an arrow (but is later healed).
Clarisse is seen talking to her father on the CSS Birmingham. Clarisse is never shown talking to her dad.
Annabeth hears the Siren from their island and learns her fatal flaw. Annabeth's fatal flaw is never mentioned. The Sirens appear as patrons at a cafe that they stop at that serves coffee and nectar
Annabeth is severely wounded by Polyphemus during their fight and is healed by the Golden Fleece. The Manticore fatally wounds and kills Annabeth with his spikes, but she is revived by the power of the fleece.
Chris Rodriguez is one of the only known demigods working for Luke in The Sea of Monsters. Chris Rodriguez, Ethan Nakamura, and Silena Beauregard are all referenced and shown on the Andromeda as servants of Luke.
Polyphemus' Sheep help defend the fleece by eating anything that gets too close, except for Polyphemus himself or another cyclops. Polyphemus' Sheep do not make an appearance in the film, but Grover mentions that Polyphemus already ate them when he ran out of things to eat.
Annabeth uses her knife and cap of invisibility to help on the quest multiple times. Her knife and cap are never seen or mentioned.
Cleaning Harpies are hired by Tantalus. A Harpy barista is seen talking to Grover at the Siren Cafe.
Annabeth's Knife is the Cursed Blade of the Prophecy. Anaklusmos is the Cursed Blade of the Prophecy.
There is no technology allowed at Camp Half-Blood. Annabeth uses an iPad to find ways to heal Thalia's Pine Tree.
There are two Colchis Bulls. There is only one Colchis Bull.
Tyson said "Bad Cow" to the Colchis Bull. Tyson said "Bad Bull" to the Colchis Bull.
Annabeth summoned the Chariot of Damnation by throwing a golden drachma into the streets. Annabeth summoned the Chariot of Damnation by whistling.
Clarisse decides to go on the quest on her own, instead of electing the two people that she is allowed to bring along. Clarisse is assigned a satyr to help her during her quest.
Nectar is a drink used to heal demigods. Drinking too much can result in spontaneous combustion Nectar is sold as a demigod drink at the Siren cafe. "You haven't lived until you have nectar."