Developed for the 10th anniversary of the series, Wild Arms 5 follows a group of young travelers as they fight for their dying land. Players guide the rag-tag bunch of heroes through a 3D world full of adventure and combat. While jumping, sliding, and stomping through the environment to complete the main objective, gamers can also engage in mini-games and side quests for money and rare items. Although the story revolves around new characters, the HEX battle system returns and several known avatars make cameo appearances during the game. Duel-pistol wielding skills make their debut in Wild Arms 5, and allow gamers to shoot different bullets that solve puzzles located throughout the adventure.

Like every game in the Wild Arms series, Wild Arms 5 takes place on the world of Filgaia. Humans are currently being ruled over by the Veruni, an alien race that landed on Filgaia 100 years ago. Dean Stark, the protagonist of the story, lives in a secluded village away from all the turmoil. He dreams of one day leaving the village to pursue his dream of becoming a Golem Hunter, someone who excavates ancient robots, like his idol Nightburn. While in the mountains, Dean and his childhood friend Rebecca spot a Golem's arm fall from the sky and land in a cave just in front of them. Upon entering the cave, they find a girl curled up within the Golem's hand. The girl only remembers two things, her name (Avril), and the words Johnny Appleseed. After receiving the pair of ARMs (special guns) she was holding, Dean, along with Avril and Rebecca, decides to embark on an adventure to find out what the words "Johnny Appleseed" really mean.

Meanwhile, a revolt has begun within the Veruni government. A man named Volsung has overthrown the leader of the Radical faction, sworn enemies of the more peaceful Moderater faction, claiming that his violent actions are necessary for the survival of the Veruni.