Mail processing for Lexington is scheduled to be moved to Louisville and Knoxville next year.
The U.S. Postal Service said the processing center on Nandino Boulevard is among 82 facilities nationwide that are planned for "consolidation" in 2015.
About 290 Lexington employees would be affected, said David Walton, a spokesman for the postal service.
The postal service said the coming consolidations will begin in early January and should be finished by fall 2015.
Walton said employees, business customers and members of Congress were told of the plans June 30.
In 2011, when the postal service began discussing the possibility of moving mail processing out of Lexington, the plan was met with an outcry from the public and from local postal-service employees.
It appeared in early 2012 that the Nandino facility had been given a reprieve.
But on Tuesday, Walton said, "It is going to be consolidated. That plant was approved for consolidation ... We just never implemented it."
The processing and distribution center in Paducah is also among those scheduled to be closed next year. Paducah's processing would be done in Evansville, Ind., under the postal service's plan.
After the 82 facilities have been closed, the postal service estimates that 44 percent of its first-class mail will be delivered in three days; 35 percent would be delivered in two days; and 20 percent would be delivered overnight.
Walton said 141 plants were closed in 2012 and 2013, and no employees were laid off as part of those transitions. Instead, he said, they were moved or were given other positions.
The postal service said in an online list of questions and answers that it did not implement all of its nationwide plan at once because officials "wanted to ensure efficient operations of our network" before moving to the second round of consolidations.
In a statement provided to the media, the postal service said that the 141 consolidations already completed were "highly successful" and "resulted in negligible service impact."
Those closings are saving the postal service about $865 million a year.
Kentucky processing facilities that have already been shut down include Ashland, Campton, Elizabethtown, Hazard, London, Owensboro, Pikeville and Somerset.
Consolidating processing at the next 82 facilities is expected to save about $750 million a year, or $3.7 billion over the next five years, the postal service said.
The agency, which receives no taxpayer funding for operating costs, has recorded $26 billion in losses over the past three years and says it is facing pressure from declining volumes of first-class mail, rising operating costs, wage and benefit inflation, and other challenges.
"Moreover, the uncertainty regarding legislative reform and review of postal rates in the courts continues to delay needed capital investments in network operations and undermine the future financial viability of the Postal Service," according to the media statement.