Brees, now at plus-135, had become the favorite during the Saints' 10-game win streak.
"Mahomes [was] 66-to-1 and is now -155. That'll tell you something right there," DraftKings director of sportsbook operations Johnny Avello told ESPN's Doug Kezirian, adding that Mahomes presents the largest liability to the house. "You have to look at what [opponents] he has, moving forward. Chargers. Seahawks. Raiders. It looks like he should be able to add to the stats."
Mahomes leads the NFL in passing yards (4,300) and passing touchdowns (43), and is poised to become the NFL's youngest MVP since 23-year-old Dan Marino in 1984. Typically, established stars win this award, and the 39-year-old Brees is still very much in the race, especially given he has never hoisted the MVP trophy.
"Brees' stats are really good," Avello said. "This is voted on, so could be some sentimental reasons in here for Brees."
Mahomes had become the betting favorite after Week 4 and lost that distinction after Week 11, when the Chiefs lost at the Los Angeles Rams on Monday Night Football.
He is just the latest long shot who has posed a threat to sportsbooks. Oklahoma's Kyler Murray won the Heisman Trophy last weekend as a 30-1 underdog from the offseason.
"[Award futures] are some of the toughest odds to make. It seems like when [sportsbooks] make money, you make a little. When you lose, you lose pretty significantly," Avello said. "The bettors get a handle on somebody early in the game, like Mahomes and Lamar Jackson [2016 Heisman Trophy winner as a 100-1 long shot], and they get them at a decent price."
Quarterback Philip Rivers (25-1) also has never won the MVP award and could make some noise with a Chargers win over the Chiefs on Thursday. With that outcome, Avello said he would reduce Rivers' odds to 7-1 and raise Mahomes' to 3-1.
Rams defensive tackle Aaron Donald has garnered some buzz with an NFL-high 16.5 sacks for an 11-2 team, but he remains a significant long shot at 50-1. New York Giants linebacker Lawrence Taylor in 1986 is the last defensive player to win the league MVP.