Bush said in a statement that Townsend "has ably guided the Homeland Security Council. She has played an integral role in the formation of the key strategies and policies my administration has used to combat terror and protect Americans."
Her departure continues an exodus of key Bush aides and confidants, with his two-term presidency in the final 15 months. Top aide Karl Rove, along with press secretary Tony Snow and senior presidential adviser Dan Bartlett, left earlier this year.
Bush in his statement early Monday noted that Townsend had served in the position for more than 4 1/2 years.
"Fran always has provided wise counsel on how best to protect the American people from the threat of terrorism," the president said. "She has been a steady leader in the effort to prevent and disrupt attacks and to better respond to natural disasters."
Townsend, who at one point had figured in speculation as to who would head the then-new Department of Homeland Security, was a familiar face, often appearing to argue the administration's position on morning news and Sunday interview shows.