In April 1, 1952, at the Norfolk Naval Shipyard in Portsmouth, Virginia USS Greene was decommissioned and received a major conversion. She was commissioned for the second time on December 1, 1952, as the first (DDR) or Destroyer Radar Picket ship. USS Greene was fitted out with special radar communications systems which enabled her to act as an early warning unit when stationed ahead of a task force. She retained her six five-inch guns and six three-inch guns, but her lighter anti-aircraft weapons were removed. Additional radar antennas were also added forward of the after gun-mount. Although USS Greene's primary focus was now anti-air warfare, both naval shore bombardment and anti-submarine warfare remained important missions.

Throughout the 1950's and into the early 1960's USS Greene's operating schedule was similar to that of other Atlantic Fleet destroyers: U. S. Second Fleet operations, U. S. Sixth Fleet operations, occasional Northern European trips and NATO operations. During early 1953 USS Greene conducted Refresher Training in Guantanamo Bay, Cuba prior to reporting to Pennsacola, Florida for duty. On September 16, 1953, She departed Norfolk, Virginia for the Mediterranean. USS Greene participated in NATO Operation "Mariner" while enroute. She returned to her home port of Norfolk, Virginia on February 3, 1954.

In January of 1954 USS Greene participated in Operation "Springboard" in the Caribbean. USS Greene became the Flagship for Commander Destroyer Division 42 on February 23, 1954. In the Summer of 1954 the "Steamin' Greene" sailed again to the Mediterranean area and visited many familiar ports. Returning to the United States she participated in inter-ship and air defense exercises in preparation for another Mediterranean tour in July of 1955. Just prior to Christmas of 1955 USS Greene returned to Norfolk, Virginia.

USS Greene headed again for the Mediterranean on July 28, 1956. During this tour of duty several anxious and eventful weeks were spent off the Suez Canal and Israel's Coast. After four months of operations USS Greene returned to home port and a few weeks later went into Norfolk Naval Shipyard, Portsmouth, Virginia for regular overhaul. Coming out of overhaul in March 1957, she was on her way again to the Mediterranean for Sixth Fleet duty. USS Greene participated in NATO exercises and rescued the two survivors of a night plane crash on the USS Roosevelt (CVA-42).

After returning to Norfolk, Virginia in October 1957, USS Greene was back in the Mediterranean in December. Christmas and New Year's Day was spent in Palma, Majorca, Spain. While returning to home port USS Greene participated in a massive air-sea search (lasting eight days) for a Navy patrol plane lost in the vicinity of the Azores. From March until June 1958 the ship's time was spent in home port and short operations off the Atlantic coast. In June USS Greene left on a Midshipman training cruise and visited Santander, Spain; Trondheim, Norway and Ghent, Belgium. In Belgium the crew had the opportunity to visit the Brussels World's Fair. The ship also took part in NATO operations off the British Isles. She returned to Norfolk, Virginia on August 8, 1958.

In November of 1958 USS Greene participated in LANTFLEX which consisted of a three week training cruise in the Atlantic. She departed from her homeward course long enough to rescue the downed pilot of a Navy F4D about fifty miles off Cape Hatteras, North Carolina.

In September 1959 the home port of USS Greene was changed to Charleston, South Carolina . Participating in the "Grand Entry" into Charleston, South Carolina USS Greene entertained various city officials and dignitaries at a reception on board. On September 1, 1959, USS Greene was assigned to Destroyer Squadron Six and became the Flagship for Commander Destroyer Division 62. She participated in a missile nose cone recovery operation on September 23, 1959, off Cape Canaveral, Florida.

On January 28, 1960, USS Greene departed for Mediterranean Sixth Fleet duty. Ports of call included: Genoa and Naples, Italy; Athens, Greece and Cannes, France. USS Greene returned to Charleston, South Carolina from the Mediterranean in September 1960. She then went to sea to train new crew members and responded whenever required to handle various "hot spots" in the Caribbean. After a year in Charleston, South Carolina, USS Greene departed once again for the Mediterranean in August 1961.

Almost all of USS Greene's entire Sixth Fleet deployment was spent escorting USS Intrepid (then CVA-11). With her superior radar and TACAN, USS Greene was stationed close to USS Intrepid to sort out the air picture and to provide aircraft guidance back to the carrier. Tensions increased in 1961 as a result of the Berlin crisis. Naval Reserve forces were "called up" and two reserve destroyers were added to the Sixth Fleet. During this Mediterranean cruise USS Greene and USS Intrepid experimented with new plane guard tactics that helped to decrease the possibility of collision during low visibility. These new tactics were adopted by the Navy several years later. In 1961 USS Greene received the Battle Efficiency "E" for outstanding performance!

Ports-of-call during this deployment included: Valletta, Malta; Thessalonika and Piraeus (Athens) Greece, Naples, Gaeta, Livorno and Genoa, Italy; Golfe d' Juan, France and Barcelona, Spain. Christmas 1961 was spent in Naples and New Years in Greta, Italy. During the transit home in February 1962, USS Greene fought through a major storm and received significant damage to her starboard side. In early March as she entered the Cooper River in Charleston, South Carolina, her berth was changed so that dependents greeting the ship would not see the ship's damage.

The Spring and Summer of 1962 found USS Greene in Guantanamo Bay, Cuba several times. Political tensions were mounting and her radar and guns were needed to help defend Guantanamo Naval Base. In October 1962 as the crew returned from weekend liberty, USS Greene lighted all boilers, checked all weapons systems and rapidly left Charleston. That evening off the coast of Florida the crew tuned in commercial radio stations and heard President Kennedy announce the Cuban Quarantine. In the spirit of USS Greene's motto,

"Affirmative, On the Way", she joined the carrier strike force off Cuba at flank speed.

USS Greene's mission during the Cuban Missile Crisis was to protect the carriers from hostile aircraft, Soviet submarines and the Soviet built OSA and KOMAR guided missile patrol boats which were operating out of Cuba. Fortunately, the crisis ended without combat and USS Greene returned to Charleston, South Carolina in November 1962 before proceeding to Boston Naval Shipyard.