The 747-400 is an improved model with increased range. It has wing-tip extensions of 6 ft (1.8 m) and winglets of 6 ft (1.8 m), which improve the 747-400's fuel efficiency by 4% compared to previous 747 versions. It has a new glass cockpit designed for a flight crew of two instead of three. The use of electronics reduced the number of dials, gauges and knobs from 971 to 365. It has tail fuel tanks, revised engines and a new interior. The longer range was used by some airlines to bypass traditional fuel stops, such as Anchorage. Powerplants include the Pratt & Whitney PW4062, General Electric CF6-80C2, and Rolls-Royce RB211-524.

The -400 was offered in passenger (-400), freighter (-400F), combi (-400C), domestic (-400D), extended range passenger (-400ER) and extended range freighter (-400ERF) versions. The freighter version does not have an extended upper deck. The 747-400D was built for short range operations and does not include winglets, but these can be retrofitted. Cruising speed is up to Mach 0.855 on different versions of the 747-400.

British Airways operates the largest fleet of 747s in the world. The addition of winglets is a noticeable difference between most -400s and earlier variants.

The passenger version first entered service in February 1989 with launch customer Northwest Airlines on the Minneapolis to Phoenix route. The combi version entered service in September 1989 with KLM. The freighter version entered service in November 1993 with Cargolux. The 747-400ERF entered service in October 2002 and the 747-400ER entered service the following month with Qantas, the only airline ever to order the passenger version. Some of the last built Boeing 747-400s were delivered with Dreamliner livery along with the modern Signature interior from the Boeing 777.

In January 2004 Boeing and Cathay Pacific launched the Boeing 747-400 Special Freighter program, later referred to as the Boeing Converted Freighter (BCF). The first 747-400BCF was redelivered in December 2005.

The last passenger version of the 747-400 was delivered in April 2005 to China Airlines. Boeing announced in March 2007 that it had no plans to produce further passenger versions of the -400.