Mary Cheney, 37, and her partner of 15 years, Heather Poe, 45, are expecting a baby, said Lea Anne McBride, a spokeswoman for the vice president. The baby is due in late spring.
"The vice president and Mrs. Cheney are looking forward with eager anticipation to the arrival of their sixth granddaughter," McBride said.
The vice president's other, older daughter, Elizabeth Cheney, is on leave as deputy assistant secretary of state after having her fifth child with her husband in July.
Mary Cheney was an aide to her father during the 2004 campaign, as was Elizabeth, and now is vice president for consumer advocacy at AOL.
McBride declined to elaborate on the circumstances of Mary Cheney's pregnancy. Mary Cheney and Poe moved from Colorado to Virginia a year ago to be closer to the Cheney family.
The Washington Post first reported the news in Wednesday's editions.