The Boeing 757-200 sported "new technology wing and engines to give the best fuel mileage of any standard-body airliner" in 1982. On a 500-mile flight, the 757-200 provided about 45 percent better fuel efficiency than the Boeing 727 it replaced in the Delta fleet. It had more seats than the Boeing 727 (187 compared to 148), and required a crew of two pilots and six flight attendants, while the older 727 required a crew of three pilots and four flight attendants.

Delta was launch customer for the PW2037 engine, which provided 10 percent more fuel efficiency than earlier JT10D Pratt & Whitney engines offered on the 757. (Note: The 757 was initially launched with Rolls Royce engines). "We felt it was worth waiting for," said Ron Allen, Delta president and CEO, when Delta's first 757 arrived in 1984. Other commercial customers for the PW2037 included Northwest Airlines, with twenty 757s on order.

A new Boeing wing design, fitted with double-slotted trailing edge flaps and full-span leading edge slats, made possible take-offs with a full passenger load with about 1,250 feet less runway than required for the advanced 727 for a 1,500 nautical-mile trip. With its new wing and high thrust engines, the 757 could cruise at a higher altitude than the advanced 727-200, allowing greater fuel savings and use of higher airways.

The 757's four-wheel main landing gear units allowed operations on runways previously closed to commercial planes of its size. Pavement loading was the same as that of the smaller 737.

Delta's innovative low-cost carrier Song, which operated from 2003-2006, flew a fleet of specially-configured Boeing 757-200s. The entire cabin was one class with leather seats and a free personal entertainment system at every seat, featuring audio MP-3 programmable selections, trivia games that could be played against other passengers, a flight tracker, and satellite television provided by the DISH Network.

At the height of its operations in 2005, Song flew 48 Boeing 757-200s to 16 locations, including Atlanta; Hartford, Connecticut; Los Angeles; Las Vegas; New York; Seattle; San Francisco; five cities in Florida and three Caribbean vacation spots—Nassau; San Juan, Puerto Rico; and Aruba. The airline operated over 200 flights a day.

Delta announced plans to fold Song into Delta's domestic operations on October 28, 2005. Song operated its last flight on April 30, 2006, and service shifted to mainline Delta on May 1, 2006.

Delta returned Song's Boeing 757 planes from one-class to two-class cabins, but expanded Song's seat-back entertainment systems and leather seats to other aircraft in the Delta fleet.

Former Song 757s started appearing on Delta's transcontinental routes in Fall 2006. The last green-and-white Song 757 was repainted in Delta livery in January 2008.

In 2007, Delta entered into leasing agreements to acquire Boeing 757-200 extended range twin-engine (ETOPS) certified aircraft. The 757-200 ETOPS could fly up to 4,520 miles or approximately 9 hours and 15 minutes of flight time, and serve Delta destinations in North America, the Caribbean, Latin America and Europe. The aircraft were equipped with winglets to reduce drag and increase fuel efficiency and range.

The 17 Boeing 757-231 and -2Q8 models, former American Airlines and TWA planes, were delivered to Delta, July 15, 2007-March 14, 2008, and assigned Ship Numbers 6801-6817. Upon delivery the planes operated with 22 first class and 158 coach class seats with interior upgrades. Beginning in December 2007, the seats were replaced with 16 BusinessElite seats and 158 slim-line seats in coach. Delta also added in-seat entertainment system and enhanced crew rest areas. Galleys and lavatories were refreshed. Rather than the standard 6 doors and 4 window exits, this version of the 757 had eight doors.

From a merger with Northwest Airlines, Delta acquired 45 Boeing 757-251s and 16 757-351s—this was Delta's first 757-300 model. Northwest merged with Delta on October 29, 2008, and the merged airline began single operations on January 31, 2009.

757s stand out as the most-decorated of the Delta fleet. See 757s in commemorative paint schemes and markings at the Special Livery timeline.