- Raphael: Casey and Raph clashed with each other as soon as they met, and grew a quick rivalry. That rivalry dissolved into friendship when they were forced to work togther, and actually saved each other from life-threatening danger. Donnie even stated that now they had two Raphael's now.
- Donatello: Casey and Donnie's relationship starts as a stormy one, due not only to both Donnie and Casey having feelings for April, but an unspoken dislike that seems to border on a "jock vs. nerd" war. Donnie does, however, seem to respect Casey being loyal and good in a fight, as Casey is equally willing to acknowledge Donnie's intelligence and technical saavy saving the day on a number of occasions. Donnie even stated that now they had two Raphael's now.
- Michelangelo: Mikey and Casey usually have fun together. In Meet Mondo Gecko, they skated together out on New York and fights Hun and the Purple Dragons together as comrades.
April O'Neil: Casey and April seem to care about each other a lot. Casey likes her as a girlfriend, much to Donatello's dismay, and she likes him as a close friend, but still likes Donnie as one more. April hangs out with Casey at school. At first, April was tutoring Casey and after sometime they became good friends. When Mutagen Man attacked them Casey became protective over April and when Mutagen Man was about to kill Casey April quickly came to his rescue and they both escaped him. When a squadron of Robot Foot Soldiers attacked them at the Midtown hockey rink, April somehow ended up leaving Casey behind and ran out of the rink as Donnie came to her rescue. She remembered about Casey as they rushed back inside only to see him alright. In Of Rats and Men when the Rat King and his army of Rats attack the city April tells Casey that he may need to sit it out because of his fear of Rats and when Casey was taken by one of the giant rats April was left distraught. When she, Casey and Irma were escaping, Casey knocked out the giant rat that was trying to attack them which seemed to have impressed April. In Wormquake! when Casey was eaten by a one of the giant space worms April was grieving over him but was surprised and excited that he was alive and was even more happy when she and Donnie saved him from the worm. Although it was revealed that Casey prefers to hang alone with April, he is seen to hang out with her and the turtles in many episodes.
Master Splinter: Casey and Splinter interacted very little because Casey is sometimes uncomfortable around him, due to his fear of rats.
- Slash: Casey was commented by Slash that Raph found a good partner in him and later turned against Newtralizer to protect him for Raph.
Mondo Gecko: Casey at first did not trust Mondo due to his alliance with Fishface, but after seeing him rescue him he grows to like him.
The Purple Dragons: Casey fights the Purple Dragons in someplaces (The bank, the muesem or the alley).
- Hun: Casey encounters Hun when the criminal and the Purple Dragons were robbing a bank.
The Kraang: Casey faces the Kraang in someplaces. (The sewers, the city, etc.) The enemy of the Turtles makes them the enemy of Casey Jones.
- Kraang Prime: Casey encounters Kraang Prime when she was mutating the people of New York in The Invasion.
- Kraang Subprime: Casey and Irma have been introduced at school, but he never encounters her as Kraang Subprime because he was on the surface in The Invasion and had to stay at Antonio's Pizza-Rama in Battle For New York.
The Foot Clan: One of Casey's most dastardly enemies. He encounters two of their robot ninja at an ice rink during his tutoring sessions with April. Aware that they want April, he holds them back her while she goes out and calls Donnie to come and save her.
- Shredder: Casey encounters Shredder at the Auman chemicals factory and attempts to fight him but Shredder is unstoppable for Casey.
- Tiger Claw: Casey encounters Tiger Claw when he and April had a Kraathatrogon swallow him so he can be sucked into the Kraang portal while inside it. When Tiger Claw returns, he goes after Casey, who asked if he is still upset about "the worm thing", and badly bruises him.
- Stockman-Fly: Casey encounters Stockman-Fly when he, Donnie and Leo came to stop him from dropping April into his mutagen tank. Afterwards, Casey rides with April on her dad's back and helps them keep Stockman-Fly from getting his hands on Donnie's retromutagen.
- Bebop and Rocksteady: First, Casey encounters Rocksteady when he and Raph were searching for Karai at the theatre, but is no match for him and captured. Afterwards, he encounters an invisible Bebop at the funhouse when helping Donnie and April get to Karai before he does. Donnie throws a smoke bomb at Bebop, giving Casey enough time to kick him out of the house.
- Rahzar and Fishface: Casey encounters Rahzar and Fishface at the docks while they were searching for chemical ingredients. They attempted to finish him off, but Raph comes to his rescue.