The western terminus of Highway 212 is at the Montana/Wyoming state line within Yellowstone National Park. Within the park it is contiguous with Northeast Entrance Road, which has its western terminus on the Grand Loop within the Wyoming portion of the park. Highway 212 passes through Cooke City, Montana, then crosses the Wyoming state line and re-emerges into Montana approximately later. The section of Highway 212 between Cooke City, Montana and Red Lodge, Montana is known as the Beartooth Highway. Rising to an elevation of above sea level at Beartooth Pass, the highway traces the historical route of Civil War General Philip Sherman over the Beartooth Mountains. In his book Dateline America published in 1979, the late CBS correspondent Charles Kuralt referred to the highway as "the most beautiful drive in America."
Running northeast from the Beartooth Mountains, Highway 212 joins U.S. Route 310 before passing into the town of Laurel, Montana. Here Highways 212 joins Interstate 90 eastbound, while Highway 310 ends. Together, Highway 212 and I-90 run east to the city of Billings, Montana between mile markers 434 and 510, a distance of .
Within the Crow Indian Reservation, Highway 212 leaves I-90 and runs east and southeast through the high plains of Montana. It is the main east–west road through the Northern Cheyenne Indian Reservation. Southeast of Alzada, Montana, Highway 212 recrosses the Wyoming state line; after about , Highway 212 enters South Dakota. For the entire length of Highway 212 in Montana between I-90 and the Wyoming state line, it is also known as the Warrior Trail Highway.
The 160 miles of Highway 212 in Minnesota are officially designated Minnesota Veterans Memorial Highway. Yellowstone Trail is the original name designation for this same stretch of U.S. 212 from the auto trail days. Yellowstone Trail was one of the first designated names written into law in the state, but not now marked anywhere along the Minnesota portion of U.S. 212.
On April 29, 2002, former U.S. Transportation Secretary Norman Mineta was in the Twin Cities for an announcement regarding transportation in Minnesota. Mineta presented a $2.9 million check (Federal Highway Administration grant) to state transportation officials. The $2.9 million is part of the $238 million funding for the new 12-mile freeway alignment of U.S. Highway 212 in Eden Prairie, Chanhassen, and Chaska.
The groundbreaking celebration on August 20, 2005, was held in Chaska. Elected officials at the ceremony included U.S. Senator Norm Coleman, former U.S. Rep. Mark Kennedy, U.S. Rep. John Kline, U.S. Rep. Jim Ramstad and Lieutenant Governor Carol Molnau.
Lieutenant Governor and Transportation Commissioner Carol Molnau said, "When the Legislature approved the $900 million Transportation Finance Bill secured by the Pawlenty Administration during 2003, we were able to advance Highway 212 as a 'design-build' project by eight years from its originally scheduled start between 2010 and 2015."
Counties and cities along the route are lobbying to extend the four lane divided highway even farther. U.S. Highway 212 widens to four lanes near Cologne but then drops back to two lanes at Norwood Young America, where it widens to four lanes again west of town. MnDoT is considering the proposal.