Maryland officials had fought the move of the ship, whose missions have included supporting service members in Iraq and helping earthquake victims in Haiti.
Former Rep. Helen Delich Bentley, who helped to bring the ship to Baltimore in the 1980s and worked with the current congressional delegation to keep it, called the decision a symbolic and an economic blow to the region.
"The Comfort, and what happens with it here, probably generates a conservative 35, 40 million dollars a year," said Bentley, a consultant to the Maryland Port Administration and the port of Baltimore. "That will be lost."
The U.S. Fleet Forces Command said the move from a commercial lay-up berth in Canton to a secure military pier at Naval Station Norfolk would save $1.7 million in the first year and $2.1 million a year after that.
"The Navy alleges that it will be cheaper in Norfolk," Bentley said. "We don't agree with that. But we weren't able to prove it."
A spokeswoman for Gov. Martin O'Malley said the governor had discussed the Comfort with Navy Secretary Ray Mabus.
"We are looking at the potential impact, but certainly understand the cost-cutting that is happening at every level of government," spokeswoman Raquel Guillory said.
The Fleet Forces Command said the transfer would allow the ship to make better use of the naval logistics hub and industrial base in Norfolk, move the military members assigned to the ship closer to other military facilities, and position the vessel nearer to the open sea.
The Comfort's current contract with Keystone Ship Berthing continues through May 2013. The Navy plans to transfer the vessel on or around March 1, 2013.
Converted from an oil tanker to a 1,000-bed medical center in 1987, the 894-foot vessel employs 18 civilians and 59 naval personnel.
For deployments, it takes on additional civilian crew members and draws on physicians, nurses, technicians and other staff from the Walter Reed National Naval Medical Center in Bethesda, the Naval Academy and Naval Air Station Patuxent River in St. Mary's County.
The Navy had berthed the Comfort in Baltimore, which is a half-day's sail from the open ocean, in part for its proximity to the Bethesda medical center. A move to Norfolk would put the ship within a few miles of the Naval Medical Center Portsmouth and at the edge of the Atlantic Ocean.
Officially, the mission of the Comfort is to provide emergency medical and surgical care for U.S. troops in combat. It deployed to the Persian Gulf War in 1991 and the Iraq War in 2003.
But the Comfort generally has proved too slow and cumbersome to be useful as an emergency hospital. In recent years it has been used primarily for humanitarian relief missions.
The ship's medical crew treated nearly 1,000 survivors of the 2010 earthquake in Haiti during a two-month mission. It also responded to the attacks of Sept. 11, 2001, in New York and Hurricane Katrina in New Orleans in 2005.
The ship returned in September from a five-month humanitarian mission to nine countries in the Caribbean and Central and South America.
Maryland officials had fought the move to Norfolk for at least 18 months. The Navy sought $10 million in 2010 to upgrade a pier in Norfolk to accommodate the ship when its Keystone contract expired.
Only two years earlier, the Navy had paid $5 million to upgrade the Comfort's Canton berth. The Navy has paid Keystone $1 million annually to keep the ship in Baltimore.