Throughout the franchise (particularly early episodes), Jimmy has had a crush on Betty Quinlan, who is one of his best friends and Jimmy repeatedly tries to impress her with his inventions. Unfortunately, Jimmy's inventions backfire and as usual, he has to fix his mistakes.
They continuously flirt with each other, much to Cindy's envy and sadness. It is hinted that Betty might have had some interest in Jimmy, but knows that he belongs with Cindy instead and is fully supportive of it, but it's hard to show it because Cindy is always mean to her.
In a a planned episode for season four, Cindy and Betty would've finally become friends after working together to escape Jimmy's lab. It is also worth noting that Cindy would've finally come clean about about her true feelings towards Betty.
- In Party at Neutron's, Jimmy decides to throw a party while his parents are away to impress Betty and his friends. When things get out of hand, Jimmy demands everyone to leave, but he turns around and sees Betty and decides to continue the party. Unfortunately, Jimmy's parents are coming home early (due to Hugh destroying the play's set) and he uses the time accelerator to end the party quickly. When everyone leaves, Betty kisses Jimmy on the cheek.
- In Operation: Rescue Jet Fusion, she appears in Jimmy's dream sequence as his leading lady.
- In The Great Egg Heist, Jimmy accidentally shows a hologram projection of her blowing kisses.
- In Out, Darn Spotlight, he tries to audition for the school play so he can be with Betty, but he doesn't get a part and becomes stage technician, so he makes real special effects to impress her. During rehearsal, he intentionally interrupts her and Nick's kissing scene. When Nick is injured, Jimmy is to take his place. Just as Jimmy and Betty are about to kiss, Sheen causes a twister to emerge and send the school flying. Luckily, Jimmy saves them, then Betty approaches him and complements what he did, then kisses him on the lips to make up for that scene not happening on stage.
- In Send in the Clones, Betty seems to flirt back to Cool Jimmy, who she most likely believes to just be the real Jimmy.
- In One of Us, Jimmy is seen photo editing pictures of the two of them into a wedding photo. Jimmy decides to go to Betty's house for investigation on Grandma Taters' show (and so he could be with her), but he runs away when she is turned into a zombie.
- In Vanishing Act, Jimmy puts on a magic show to impress her. This is when Cindy's jealousy reaches critical mass and she causes Jimmy's magic box to overload and send her, Betty, Carl and Sheen into another dimension. Cindy yells at Betty and blames her and Jimmy for what happened, and Jimmy reminds Cindy that she was responsible, but Cindy makes up an excuse. Before Jimmy can say anything else, Betty pulls Cindy aside to have a talk with her, and she explains that she knows about Cindy and Jimmy's interest in each other, and that Cindy can have him.
- In League of Villains, we learn that Jimmy has been storing a drawer full of pictures of Betty in his lab, one of which was left sitting out by his main computer. After seeing this, Cindy made Jimmy get rid of all of the pictures, but Jimmy having them shows that he wasn't completely over Betty at the end of the series.