When Blue is defeated, the player will be able to enter the Captain's quarters, where they will find him seasick. By choosing to help him by giving him a backrub, players will be able to get HM01 (Cut).
Once the captain is healed, the S.S. Anne will sail away the moment player exits the ship. Although it is said to return once a year, none of the games in which it appears have a time system capable of measuring this, and the ship will not be seen again. The only way in which one can get the ship to remain is by losing a battle and blacking out, thus returning to the Pokémon Center (or using a Generation I glitch).
As the player cannot return to the ship once it has left, all of the items on the ship and in the port can be permanently missed without ever obtaining them.
In Pokémon Red, Blue, and Yellow, as well as their remakes FireRed and LeafGreen, a truck was placed in the S.S. Anne's port, which seems to serve no evident purpose except as scenery, and was programmed into the game as a floor tile. With scenery being very sparse in the Generation I games, and this being one of the few sprites with no other purpose than to exist in one spot, fans began speculating that another purpose existed for this truck. The truck cannot be accessed without Surf, which the player would not normally have or be able to use before the S.S. Anne departs.
There are a couple of ways the player can access the truck. One is to lose a battle on the S.S. Anne after obtaining HM01 (Cut) so that the player is warped to the last Pokémon Center they visited without the S.S. Anne departing and they can return later with Surf. Another is to trade in a Pokémon that knows Cut, so that there is no need to obtain HM01 (Cut). Alternatively, a glitch in Generation I also allows the player to bypass the sailor who normally blocks the entrance after the ship has departed.
A rumor claimed that the truck could be moved with Strength and Mew could be found underneath it. This rumor is untrue. In Generation I, there is nothing to be found around the truck at all, but in FireRed and LeafGreen, a Lava Cookie is hidden to the south of the truck.
A Beauty in Pokémon XD: Gale of Darkness's Quick Battle Mode in the Vs. Mode makes a reference to the truck before the battle starts with a line from a song she is writing: "There's no Pokémon under a truck, maybe you'll just find a Muk!"
After the S.S. Anne leaves Vermilion City, it never returns. However, in the Generation I games, one rumor claimed that if the player defeated the Elite Four 365 times, the ship would return with more powerful opponents on board, due to an NPC in Red and Blue explaining that the ship was a luxury liner for Trainers that visited Vermilion once a year. However, this rumor is untrue.
Out on the open ocean, Team Rocket, including Jessie, James, Meowth, and a number of Team Rocket Grunts began taking the Pokémon of everyone else on board the St. Anne by force. Ash led a counterattack against the Rockets, leading to a large battle and many of the members of Team Rocket being 'blasted off' through the side of the ship.
Afterwards, the St. Anne started taking on water, and the passengers had to be evacuated. Ash delayed the evacuation to trade back the Raticate for his Butterfree, but the moment Ash obtained Butterfree's Poké Ball, the ship jerked and the Poké Ball bounces out of his hand, while at the same moment James' Magikarp's Poké Ball bounced out of his hand. When both Ash and James went back to go get their Poké Balls, the ship jerked once more and knocked out Ash, his friends, and the Team Rocket trio. When they awoke, the St. Anne was upside down and underwater, balancing on a seamount.
The two groups fought at first, but Misty took charge and began directing all of them in an emergency escape plan before the ship fell into the depths of the sea floor. Since the ship was upside down, they would need to escape through the thinnest point in its hull, which Misty knew was in the engine room, having built a model of the ship herself. They made their way through the ship to this point, and then Ash ordered his Charmander to burn a hole in the hull. With the help of Squirtle, Goldeen and Starmie, Ash and his friends were able to swim to safety, while Team Rocket nearly drowned since all they had to rely on was James's Magikarp, which could only Splash around on the floor.
Once everyone was off-board, the St. Anne's balance tilted, and it fell off the seamount, down towards the abyss, never to be seen again.
In the special The Search for the Legend, Ritchie rode aboard a ship called the S.S. Anne in the dub; the ship is unnamed in the original Japanese. However, it was named the S.S. Anne rather than St. Anne.
The Japanese word 号gō, in this context, means "model"; however, it is a Japanese-only descriptor and is not meant to be translated. The English localization uses the equivalent "S.S.", short for steamship, and drops "St." from the name.