"I've tried poor but happy, wasn't that happy!" - Gabrielle Solis (Eva Longoria

Betty Applewhite is the first African-American housewife who begins a recurring role in the final two episodes of the show's first season. Betty Applewhite is a single mother, with strong religious beliefs and is a former concert pianist. On the first episode of Season 2, she agrees to be the organist at Rex van de Kamp's funeral on the request of Bree.

She is a seemingly smart woman not be trifled with, as revealed in the subsequent unpleasant and threatening exchanges with Bree van de Kamp. Her reasons for moving from Chicago to Wisteria Lane are mysterious and rather quick due to the fact she has locked up her son (Caleb) in her basement. She bought the Wisteria Lane house over the phone and had moved in in the middle of the night, arousing the suspicions of the housewives thereafter. She eventually revealed to Bree van de Kamp that Caleb had murdered Matthew's girlfriend at a local lumberyard.

Meanwhile, her son Matthew has been dating Danielle Van De Kamp, the daughter of Bree Van De Kamp. Matthew wants a 'normal life'. A life without the secrets and pressures of keeping a convict out of sight. Together, he and Danielle hatch a scheme to have Caleb put down. Matthew tricks his brother into going over to Danielle's house to rape her. Bree finds out and informs Betty that she will call the cops and send Caleb away forever. Betty will not have this and decides to poison Caleb because she refuses to have him locked away. By poisoning him she will be giving him peace, a better life because in her own words: "He deserves so much better than this".

Betty takes Caleb on a picnic where she treats him to a bowl of ice cream in which she has poisoned. While holding back tears she tells her son that Matthew stayed home because it was a special day just for the two of them. Caleb asks if Matthew is mad with him and Betty asks why. It is then that she learns the horrible truth when he spills the beans of what really went down. Betty immediately grabs Caleb's hand and stops him from eating the ice cream. When she arrives back on Wisteria Lane, she tricks Matthew into going into the basement where she locks him in for punishment.

Danielle later comes to Matthew's aid and strikes Betty with a crowbar. The two fled while an unconscious Betty Applewhite is left on the basement floor.

After she comes to, Betty decides that leaving Wisteria Lane once and for all will do her some justice. She packs up all of her belongings and leaves her house with Caleb in the middle of the night. Betty tells him that for now on it'll be just the two of them. That's when the police show up and have her arrested in front of the many watchful eyes of the neighbors of Wisteria Lane.

It is in jail that Betty learns that it wasn't Caleb behind Melanie Foster's murder...it was Matthew. Betty calls Bree who is in a psychiatric hospital and warns her that they need to get Danielle to safety right away. As Bree escapes the hospital, Matthew and Danielle head back to the neighborhood to grab some things. While Danielle attempts to break into her mother's safe, Matthew heads back to the Applewhite home to pick up some cash for his new life with her. Betty has been waiting here to confront him...and confront him she does. She reveals that she has learned the shocking truth and is even more shocked that he has placed the blame on his own brother.

According to Matthew, Betty Applewhite loved Caleb more than she loved him. Betty argued that she was the only person that Caleb was going to receive love from. Matthew leaves to go get Danielle from her house before Betty alerts the authorities.

There is a confrontation with Bree Van De Kamp as Matthew holds her at gunpoint. Danielle is exposed to the man Matthew really is and just as he is about to pull the trigger, he is killed, the victim of a bullet straight to the heart from the gun of a SWAT team policeman. Betty and Caleb watch as his lifeless body is wheeled away and Betty decides that this dark chapter of her life is over and done with.

Betty Applewhite finishes packing all of her things into a large moving truck and she and Caleb leave Wisteria Lane once and for all, never looking back, and pressing on to a more peaceful and serene future, one without the juicy drama.