Cacnea was caught by James in the episode A Poached Ego!. In the episode, Team Rocket found a group of Ekans and Koffing being hunted by a Pokémon poacher; Jessie and James permanently released their Arbok and Weezing to protect the Ekans and Koffing. Before releasing Arbok and Weezing, Team Rocket had been chased by some Beedrill because they had landed in the Beedrill's nesting place. Cacnea had been walking by. When it saw that they were in need of help, it used Pin Missile to drive the Beedrill away. In gratitude, James gave it a bag of cookies. However, the bag was closed. Later, after defeating the poacher, Team Rocket encountered Cacnea on a road. It gave James the bag, and James opened the bag and gave Cacnea a cookie. James then asked Cacnea if it would like to join him, and it agreed, jumping into his arms and hurting him with its spikes.
Cacnea was James's fighting Pokémon throughout all of Hoenn.
In Seeing is Believing!, Cacnea was used to battle Jessie's Cascoon in order to raise her experience so she would evolve. Even though Cascoon won she remained the same. Cacnea was later used in the fight against Ash and his friends, where Cascoon evolved into Dustox.
In The Bicker the Better, Cacnea was used in a Double Battle along with Seviper against Oscar and Andi and their Nidoking and Nidoqueen. Seviper ends up using Wrap on Cacnea, which causes Jessie and James to argue, allowing Oscar and Andi to take the win with dual Hyper Beam attacks, sending Team Rocket flying. Team Rocket later encounters Ash and May and agree to do a tag battle with them, with Ash using Corphish and May using Skitty. Cacnea and Corphish end up working well together and begin to get an advantage over the other two. Jessie soon sends out Dustox to help win and the battle quickly grows out of control when attacks start to fly undirected. Meowth then takes the opportunity to try to capture Pikachu and has Seviper and Cacnea use Haze and Sandstorm. Pikachu is rescued and Team Rocket is sent blasting off.
In The Saffron Con, Jessie wanted to enter the Saffron CityPokémon Contest and asked James if she could borrow Cacnea for it. James agreed and Jessie called out Cacnea in an attempt to bond with it, but it was immediately frightened of her and jumped onto James. James desperately tried to break its embrace and Cacnea reluctantly jumped onto Jessie and became tangled up in her hair. Later that night Jessie and Cacnea agreed to enter the Contest together, even though they had to cut Jessie's hair to get Cacnea unstuck.
In A Hurdle for Squirtle, Jessie used Cacnea in the Appeals Round of the Saffron Contest. Cacnea and Jessie started by running toward each other and hugging. The painful embrace moved the crowd to tears in reaction to how close Jessie and Cacnea seemed to be. Jessie told Cacnea to use Pin Missile and the pins wind upward and collide, creating an explosion similar to that of fireworks. Both Meowth and James were amazed at Jessie's performance. Lilian then went to congratulate Jessie but noticed that Cacnea was still attached to her and she was not moving at all. Lilian tapped her and Jessie fell to the floor, paralyzed with pain. Jessie was then rushed back into the operating room by Chansey.
In Sinnoh, it was replaced as James's main battler by Carnivine. However, it was used alongside Seviper, Dustox, and Carnivine in several all out battles against Ash and his friends and to guard the Flying-type Pokémon that Team Rocket stole in A Staravia is Born!. It was only seen battling without Carnivine a few times in Sinnoh. It and Carnivine hurt James a lot in Sinnoh because they both tended to be affectionate at the same time. Cacnea was used often in Sinnoh similarly to Jessie's Seviper as Team Rocket's escapist rogue via the use of Sandstorm.
In Once There Were Greenfields, Gardenia and James battled Ash and Dawn. Gardenia told James to tell Cacnea to use Drain Punch, but James said the Pokémon didn't know that move. Through her explanation on how to do it, he did it anyway, and Cacnea pulled off the move. However, it was unable to duplicate the success. Through Meowth, Cacnea explained that the first Drain Punch was only a fluke. Gardenia suggested that James give Cacnea to her to train. He originally declined, but in the end, he realized that his lack of skill would only hold Cacnea back from its full potential. Therefore, he left Cacnea with the Gym Leader to become stronger.
To James's frustration, each time it was called out to battle, Cacnea would instead affectionately embrace its master, instead of focusing on the task at hand. When it did battle, it was fairly formidable, but usually lost to Ash or one of his friends. Like most of James's Pokémon, Cacnea had a great relationship with him and strived to please him. Cacnea is shown to be extremely loyal to James, demonstrated in Sweet Baby James, when James ordered Cacnea to attack Seviper and it did so without hesitation.