Sussex Police has issued an appeal for witnesses after the two-car collision at Fairmile Bottom, Madehurst near Slindon.
Emergency services were called to the scene just after 12.30pm.
"The driver of one of the cars, a woman in her eighties, was sadly confirmed deceased at the scene," a police spokesperson said.
"The man driving the other car was taken to hospital to be treated for injuries. Nobody else was reported involved."
The A29 was closed in both directions whilst the incident was ongoing.
The spokesperson added: "Drivers are thanked for their patience and understanding over the inevitable delays that resulted.
"Anyone who saw what happened is asked to contact Sussex Police either via [email protected] or by calling 101, quoting Operation Dordrecht."