The race - bringing together downhill and slalom pairings with one run in each discipline - will be held on Cortina d'Ampezzo's Olimpia delle Tofane piste on Tuesday.
Johnson, who on Sunday added Olympic gold to the world title she won last year, is the top pick to partner Shiffrin, the dominant slalom skier with seven wins from eight World Cup races this season.
Teammate Lindsey Vonn, who leads the World Cup downhill standings with five podiums in five races, including two wins, would have been the frontrunner a month ago but broke her leg in Sunday's downhill after seriously injuring her knee a week earlier.
While Shiffrin has won a record 108 World Cup races, Johnson has yet to win one but holds the two biggest titles of any skier's career.
Any medal would be Shiffrin's first since the 2018 PyeongChang Games, and career fourth, after she drew a blank in Beijing four years ago.
Shiffrin and Johnson also won gold at last year's world championships but, apart from Sunday's race, the downhiller has stood on the World Cup podium only once this season, and that was third in a super-G last month.
The event is being held for the first time at the Winter Olympics in the team format. Shiffrin is also competing in slalom and giant slalom.
The USA pairings are based on results, with the top downhiller and top slalom skiers together, and each country allowed four pairs.
Jackie Wiles (downhill) and Paula Moltzan (slalom) will be the USA's second pairing, with Bella Wright (downhill) and Nina O’Brien (slalom) the third and Keely Cashman (downhill) and AJ Hurt (slalom) the fourth.
Check out the full Olympic Games schedule and medal standings here!