The aircraft commander or agent shall request clearance or permission to depart for aircraft of scheduled airlines covered by this subpart.
(a) Clearance at other than airport of final departure. Aircraft may clear at each airport where merchandise and/or passengers are taken on board for transport outside of the U.S. The clearance applies only to the merchandise and passengers boarding at each place. Clearance shall be requested at the Customs port of entry (regardless of whether it is an international airport) nearest to the place where merchandise and/or passengers are taken on board.
(b) Clearance at final departure airport. Clearance or permission to depart may be requested at the Customs port of entry (regardless of whether it is an international airport) nearest the last departure airport.
ACE rules page: Part 122 in plain English