The 59-year-old Portuguese has been in the job since taking over from Otto Rehhagel in 2010.
"A short while ago I informed the Hellenic Football Federation (EPO) board that Mr. Santos will end his tenure with the national team after our commitments in the World Cup" EPO president Giorgos Sarris said in a statement.
"It is obvious that, regardless of his decision, Mr. Santos still enjoys our respect.
"The federation will support him until the last day in the job in exactly the same way we have done in the period he has guided us to 12th position in the world and eighth in Europe."
Greece will face Colombia, Ivory Coast and Japan in Group C in the finals and they begin their countdown to the World Cup with a friendly against fellow qualifiers South Korea next week.
After taking over from Rehhagel, who led Greece to their surprising Euro 2004 triumph, Santos built on Rehhagel's strong foundations, blooding many young players and has so far recorded 24 wins, 13 draws and only four defeats while in charge.
The former AEK Athens, Panathinaikos and PAOK Salonica coach guided Greece to Euro 2012 by finishing top of the qualifying group with an unbeaten run of 16 matches before their eventual quarter-final exit.
(Editing by Martyn Herman) nL3N0LW3DY
