There are some strong candidates to pull off upsets in Week 6 of the 2021 NFL season. Three first-place teams are underdogs. More than half of games with a true home team feature a road favorite.

Here are the best upset picks for Week 6 with betting odds from FanDuel Sportsbook.

Detroit Lions (+138) vs. Cincinnati Bengals

The NFC’s only winless team, Detroit has been seconds away from earning its first victory on multiple occasions. Maybe the Lions can finally get over the hump Sunday when they host a Bengals team that continues to play in nail-biters.

The Lions suffered another heartbreaker in Week 5 when they took a one-point lead over the Vikings with 37 seconds left, only to lose on a last-second field goal. Detroit has actually lost two games by a score of 19-17 on field goals as time expired.

Cincinnati has played two overtime games and two other contests decided by three points. The Bengals have yet to score more than 24 points in regulation. Joe Burrow has been mistake-prone with six interceptions in his last four games. It’s still difficult to have confidence in the Bengals as road favorites. 

Los Angeles Chargers (+144) at Baltimore Ravens 

Los Angeles looks like a real Super Bowl contender, coming off an impressive 47-42 win over Cleveland. The Chargers can certainly win in Baltimore against a Ravens team that has narrowly escaped a couple of upsets already.

Justin Herbert might be the NFL MVP through five weeks. The second-year quarterback ranks in the top five in passing yards, touchdowns and QBR. Herbert made up for a poor defensive effort in Week 5 with four touchdowns and no interceptions. Prior to Week 5, Los Angeles hadn’t given up more than 24 points in a game despite facing three of the league’s most high-powered offenses.

The Chargers’ only loss came on a last-second, 56-yard field goal against the 4-1 Cowboys. Los Angeles has already upset Kansas City on the road. Baltimore needed a fourth-quarterback comeback and overtime to beat the visiting Colts Monday night. The Ravens are only a few weeks removed from holding off the Lions with a record-setting field goal. 

Tennessee Titans (+194) vs. Buffalo Bills

Buffalo is the AFC’s hottest team. The Bills have won four straight games by at least 18 points, including a statement win in Kansas City. With the team riding high, they are susceptible to a letdown in Tennessee.

The Bills are dominating opponents with the NFL’s No. 1 defense, which has made a living off a league-high 15 takeaways. Ryan Tannehill hasn’t thrown an interception in four of his last five games. Derrick Henry hasn’t fumbled at all this season, and even Buffalo’s stout defense will have a difficult time slowing down the NFL’’s top rusher. If Julio Jones can return from his injury, the Titans might give Buffalo its biggest challenge of the season up to this point.

Tennessee blew out Buffalo 42-16 almost exactly a year ago. Josh Allen threw a pair of interceptions in the loss. Tannehill has arguably been as good as Allen in 2021, and he can match the Bills’ quarterback at home Sunday. Buffalo’s hot streak is going to end at some point. Don’t be surprised if it happens in Tennessee. 

Justin Herbert Los Angeles Chargers Justin Herbert #10 of the Los Angeles Chargers looks down field during a 49-42 win over the Cleveland Browns at SoFi Stadium on October 10, 2021 in Inglewood, California. Photo: Harry How/Getty Images