Sera Gamble, who has been co-showrunner with Robert Singer for two years, will step down in order to focus on development, according to Deadline.
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Gamble has been with the show since its debut in 2005.
Jeremy Carver has been tipped to return to Supernatural and work as co-showrunner with Singer.
Carver originally worked on the show as a writer and producer between 2007 and 2010 and left to launch the US version of Being Human, which was recently picked up for a third season.
Although there has been no official confirmation that Supernatural has been renewed, it is considered rare that a change in a show's senior production team would take place if it was not being picked up.
Gamble said earlier this year that the production team were "planning for the worst and hoping for the best", while The CW's president Mark Pedowitz said as early as last summer that he is keen for the show to continue beyond its seventh season.
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