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This article is about a character appearing in the animated series, which is not canon. You may be looking for the live-action series counterpart, if any.
She first appeared in Home when Sam and Dean wanted her opinion on the ghosts haunting their old home. She visited the house and declared that a malevolent entity was haunting the house. She also declared that the house was being haunted by not one, but two ghosts. After the events in the house, she was brought back and she declared the house to be free of any spirits and that the evil spirit was forever banished from the house. After the boys departed, she talked to John, who was hidden in the shadows. She was surprised that with all his powers, Sam could not sense his own father's presence. John tells her that it was still too soon for them to know about his arrival.
Missouri appeared in All Hell Breaks Loose - Part 2 after Sam was resurrected. She had survived an attempt on her life by demons and came to help Dean and Bobby Singer deal with Azazel, and stop him from opening the Devil's Gate. She and Bobby worked together in shutting in the gate once it had been open.