Amtrak has operated the service since 1971, using a combination of the old Great Northern, Northern Pacific and Milwaukee Road routes for the train. Amtrak originally operated it only between Chicago and Seattle. It restored the train's Portland section in 1981.

The Empire Builder route links the modernism and rustic charm of the Pacific Northwest with the hustle and bustle of Chicago and the Midwest, while passing outstanding scenery such as Puget Sound, the Columbia River Gorge, the Montana Rockies, and the Mississippi River.

The train is completely equipped with Amtrak's modern bi-level Superliner cars. It has the normal range of equipment found on long-distance Amtrak services: first-class sleeping cars with economy, deluxe, family and accessible bedrooms; a full-service dining car; a sightseer lounge with large observation windows; and standard coaches that include accessible lower-level seating. The train was Amtrak's first long-distance service to use the then-new Superliners in October 1979, and was also the first use of the new Siemens ALC-42 locomotive in February 2022.

Eastbound. the Empire Builder leaves Portland or Seattle in late afternoon. The Seattle section runs through central Washington via Wenatchee, while the Portland section travels through the Columbia River Gorge via Pasco. The two sections combine at Spokane eastbound and separate westbound.

The train's route includes the two longest railroad tunnels in the U.S. West of Wenatchee, the Seattle section passes through the 7.9-mile-long Cascade Tunnel. East of Spokane, the train runs through the seven-mile-long Flathead Tunnel between Libby and Whitefish, Mont.

Westbound, the train leaves Chicago in mid-afternoon. It takes approximately two days in each direction. En route, the train serves cities such as Everett, Vancouver and Spokane, Wash.; Sandpoint, Idaho; Whitefish and Havre, Mont.; Minot, Grand Forks and Fargo, N.D.; St. Cloud, Minneapolis/St. Paul and Winona, Minn.; and LaCrosse and Milwaukee, Wis. Amtrak added a new stop for the Seattle section at Leavenworth, Wash. in September 2009.

The Empire Builder honors James J. Hill, who built the Great Northern in the late 1800s and helped make it one of the pre-eminent railroads in the west. Hill, for his efforts to build up the GN and its associated railroads, as well as for the vast areas of the country they helped open up, earned the title, "The Empire Builder". In 2023, the train celebrated its 94th year of continuous service.