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American Airlines and JetBlue Airways said they plan to end agreements covering ticketing, baggage handling and frequent-flier programs.
The companies currently have a so-called interline agreement that allows customers to buy connecting flights on each other's planes on one ticket.
Such agreements help increase revenue as airlines can offer more destinations without having to service all the planes themselves.
The airlines will no longer accept new interline sales with each other, the companies said on Monday.
The carriers also said customers using their reciprocal frequent-flier programs would no longer earn miles or points when traveling on eligible routes, effective April 1.
The carriers did not say why they were ending the agreements.
All American Airlines' "AAdvantage" miles or JetBlue's "TrueBlue" points already accrued through this partnership will be credited to customers' accounts and will not be affected, the carriers said.
Last month, Delta Air Lines announced a major revamp of its frequent-flier program, switching to a system that ties rewards to ticket price rather than miles flown.