Gone is the traditional ceremonial start in Anchorage. Gone are the checkpoints in communities used to welcoming mushers and their dogs. Gone are the hordes of spectators who usually populate the start, the finish, and many places along the route. Gone is the route itself, or the end of it. Instead, mushers will begin in Willow, head out on the Southern Route to the Iditarod checkpoint (near Flat, a ghost town that was once a mining settlement), and then turn around and head back to Willow. The total distance this year, on what officials call the Gold Trail Route, is 860, 138 miles shorter than the usual route. Race officials said that the start would be a staggered one as well, to keep participants and volunteers from getting too close to one another.

The field is 47, a very low number the result of virus-related obstacles of travel. (One of those unable to race was last year's champion, Thomas Waerner of Norway.) As well, those who are competing must submit to coronavirus testing at regular intervals and must maintain social distancing at all checkpoints. Among that small field are four former champions: Dallas Seavey (who has won four times), Martin Buser, Pete Kaiser, and Jora Leifseth Ulsom. Top female competitors include Aliy Zirkle, a perennial top-three finisher, and Jessie Royer, who claimed third in 2019 and 2020.

The event, which began in 1973, commemorates the 1925 Serum Run a desperate delivery of life-saving medicine across the frozen wilderness to children in Nome.