The 747-400 is an improved model with increased range. It has wing-tip extensions of 6 ft (1.8 m), 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. 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.

The passenger version first entered service in February 1989 with 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 interior from the Boeing 777.

The last passenger version of the 747-400 was delivered in April 2005. Boeing announced in March 2007 that it had no plans to produce further passenger versions of the -400. However, orders for 36 -400F and -400ERF freighters were already in place at the time of the announcement.

As of October 2008, a total of 685 of the 747-400 series aircraft had been delivered. At various times, the largest 747-400 operator has been Singapore Airlines, Japan Airlines, and British Airways.