Police roadblocks prevented reporters from approaching the airport but one police officer said Madonna carried David, her adopted Malawian son, up the steps of the Gulfstream jet.
It was bound for London's Gatwick Airport, air traffic officials said, speaking on condition of anonymity because they were not authorized to speak to journalists.
The singer's lawyer has said that she will appeal against a court ruling that she is not eligible to adopt a three year old orphan girl, Chifundo "Mercy" James, because she hasn't lived in Malawi.
Madonna first spotted Mercy during a 2006 visit to an orphanage where she found David. Then, unlike now, she was able to leave the country with the infant and the adoption was completed last year.
But now Madonna is a single mother after her split from film director Guy Ritchie. Her attempts to adopt a second child caused outrage among some child welfare groups.
In a ruling Friday, Judge Esme Chombo said Madonna did not meet Malawi's strict definition of "resident." Noting that Madonna had last visited Malawi in 2008, the judge said the pop star "jetted into the country during the weekend just days prior to the hearing of this application."
Malawi requires prospective parents to live in the country for 18 to 24 months while child welfare authorities assess their suitability -- a rule that was bent when Madonna was allowed to take David to London in 2006. Madonna has two other children, Lourdes, 12, and Rocco, 8.
No date has been set for a court hearing to appeal the judge's ruling.
Madonna threw a farewell party Saturday at the luxury lodge where she was staying. Traditional dancers entertained guests including government officials and staff from Madonna's Raising Malawi charity.
The charity helps feed, educate and provide medical care for some of Malawi's more than 1 million orphans, half of whom have lost parents to AIDS.