Karen Wheeler (née Childress), portrayed by Cara Buono, is a main character in Stranger Things. She is the loving but somewhat clueless mother of Nancy, Mike, and Holly, and the wife of Ted.

In 1983, after her son's friend, Will Byers, went missing, Karen enforced strict rules that no one in her household would go outside late. This caused friction between her children, particularly Nancy. She remained largely unaware of the events around her, especially her son keeping an escaped experiment in her basement and her daughter searching for a monster from another dimension. When a group of agents arrived at their house telling her and her husband that his son and friends might be hiding the experiment, Karen became extremely distraught. She eventually tearfully reunited with Mike at the local middle school and went to the hospital where Will had been recovered.

In 1984, she remained the same; blissfully unaware of what her children were doing after they lied and say they were having a sleepover (when, in reality, Mike was tending to a possessed Will, while Nancy teamed up with Jonathan Byers to shut down Hawkins National Laboratory). She did, however, become sexually attracted to Billy Hargrove, the older brother of Max Mayfield, who reciprocated the feelings.

By the summer of 1985, Karen's desire for Billy had hit the ultimate peak, ogling him along with her friends at the local pool, where Billy worked as a lifeguard. When Billy propositioned her by offering "swimming lessons" at the local motel, Karen was about to leave for the night until she discovered Holly sleeping in Ted's lap on the chair. She realized how selfish she was and ultimately decided to not go. The next day, Karen arrived at the pool to talk to Billy (who had been possessed by another force from the dimension) and explained why she didn't come, but Billy, restraining himself from hurting her, simply told her to stay away from him. She soon resigned herself back to being a mother, offering Nancy advice after getting fired from her job, and three months later, comforting Mike after the Byers family moved out of Hawkins.

By the spring of 1986, while Mike was sent to California for Spring Break, paranoia of the town's mysterious mall fire and and recent murders of teenagers lead Karen, alongside the other parents, to believe their children to be linked to Eddie Munson, leader of the Hellfire Club, a Dungeons & Dragons club falsely believed to be a Satanic group. Karen grew to be concerned about Nancy since she was missing, and was left puzzled when Mike's friends fled from the police. Soon after, what was perceived as an earthquake caused a four-way rip throughout Hawkins, leaving Karen and the other townspeople frazzled and ready to move out. After tearfully reuniting with Mike, Karen was left to worry as she and Holly saw floating particles from the dimension, the Upside Down, beginning to infect Hawkins.