Armstrong, who won the Tour de France seven consecutive years after overcoming testicular cancer, and his girlfriend, Anna Hansen, are expecting the baby in June.
"The baby was conceived naturally," Lance Armstrong Foundation spokeswoman Rae Bazzarre said in a statement e-mailed to The Associated Press.
Armstrong had three children with his ex-wife Kristin using in vitro fertilization with sperm he had banked before undergoing chemotherapy.
"Anna and I are thrilled to confirm that we are expecting in June and our families are ecstatic and grateful," Armstrong said in a statement released Tuesday night. "We are very much looking forward to what 2009 brings on many fronts. We appreciate respecting our privacy, as we are both eager to celebrate the holidays as a family."
Three years after retiring following his last Tour de France win, Armstrong announced in September his return to competition and the Tour de France in 2009. He called his comeback an attempt to raise global awareness in his fight against cancer.
A June birth would fall between Armstrong's scheduled races in the Giro d'Italia, which runs from May 9-31 and the Tour de France, which begins July 4.