Lawrence, Kansas is notable as the city of birth of Sam and Dean Winchester, and was the home to their parents prior to the death of Mary at the hands of Azazel.

An auto repair owned by Mike Guenther, and formerly co-owned by John, exists in Lawrence. Psychic Missouri Moseley also resided in Lawrence. The late Ben Swardstrom and Meredith McDonnell, both killed by Meg, were born in Lawrence.

The main campus of the University of Kansas is also in Lawrence.

The final confrontation between the archangels Michael and Lucifer took place here. Chuck tells Dean the reason for it being there is because it has to end where it all started. It was also here that Sam and Michael got locked in Lucifer's Cage, plus where Sam woke up after being brought back.

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