In the 1970s, Boeing proposed a successor to the three-engined Boeing 727 aircraft. In the late 1970s, the final design of the 757 was decided, utilizing the same cabin cross-section as the 727/737 but with a longer fuselage, a redesigned wing and modern high-bypass fuel effficient turbofan engines. Boeing also designed a state-of-the-art advanced two-crew flightdeck with Electronic Flight Instrument System (EFIS), incorporating six cathode-ray tube (CRT) displays housing primary attitude data, navigation display and engine parameters including an automated crew alerting system. 757 incorporates two Rolls-Royce RB211, Pratt & Whitney PW2037, PW2040 or PW2043 turbofan engines.

The first operator of the Boeing 757-200 was the Eastern Airlines. The 757 programme received orders from launch carriers Eastern Airlines and British Airways in late 1978. There was an extended range version of the aircraft, the 757-200(ER) which first flew on April 8, 1986 and was delivered to Royal Brunei on May 6, 1986. In September 1987, the first Boeing 757-200(PF) was delivered to UPS. On July 15, 1988, the 757-200M first flew and was delivered to Royal Nepal Airlines.

The 757-200 was the only version of 757 available until the late 1990s. The 757-200 can carry up to 229 passengers.

On May 2, 2000 in Seattle, American Airlines announced order for 20 Boeing 757-200s and deliveries are scheduled to begin in 2001 to 2002.