The Kansas City Chiefs will head to Lucas Oil Stadium to take on the Indianapolis Colts in an extraordinary showdown on Sunday afternoon. It's time to continue our NFL odds series with a Chiefs-Colts prediction and pick.

The Chiefs defeated the Los Angeles Chargers 27-24 at Arrowhead Stadium on Thursday night football in Week 2. It was a slugfest all night, as the Chiefs struggled early and rallied back from a 10-point deficit. Patrick Mahomes completed 24 of his 35 passes for 235 yards and two touchdowns. Additionally, Clyde Edwards-Helaire rushed eight times for 74 yards while catching four passes for 44 yards. Travis Kelce caught five passes for 51 yards. 

The Colts endured a 24-0 shutout at the hands of the Jacksonville Jaguars last weekend. Matt Ryan was inefficient, completing 16 of his 30 passes for no touchdowns and three interceptions. Also, Jonathan Taylor only rushed nine times for 54 yards. Ashton Dylin led the injury-ravaged receiving core with five receptions and 79 yards, while running back Nyheim Hines caught four passes for 37 yards. 

Despite being two of the oldest teams, the Colts and Chiefs have squared off 22 times in over 50 years. Also, the Colts lead the all-time series 13-9. The last meeting took place on October 6, 2019, a game where the Colts dominated the time of possession and limited Patrick Mahomes and any heroics that followed. Mahomes completed 22 of his 39 passes for 321 yards and a touchdown in that contest. Meanwhile, Kelce caught four passes for 70 yards. The Colts produced 180 rushing yards, a good omen for a team with the best running back in football. 

Here are the Chiefs-Colts NFL odds, courtesy of FanDuel. 

NFL Odds: Chiefs-Colts Odds

Kansas City: -5.5 (-110)

Indianapolis Colts: +5.5 (-110)

Over: 50.5 (-110)

Under: 50.5 (-110)

Why The Chiefs Could Cover The Spread

Mahomes has beaten almost every team in the league, but there are four he has not, and the Colts are on that list. Significantly, he produced a 91.9 passer rating in his one match against Indianapolis but could not lead them to victory. It will be the first time Edwards-Helaire faces the Colts. However, Kelce has 11 receptions for 171 yards and a touchdown in two games against the Colts. Juju Smith-Schuster could play a role against the Colts. He has 17 receptions for 209 yards and two touchdowns over three games. The Chiefs rank second in points-per-game, sixth in passing yards-per-game, and 16th in rushing yards-per-game. 

The defense has its work cut out for them as they try and stop Taylor. However, they have already endured two good offenses and did just enough to win. Taylor is on another level, and the Chiefs must do whatever it takes to slow him down. Thus, the key for Kansas City is to put all the pressure on Ryan. 

The Chiefs will cover the spread if they can get Smith-Schuster the ball and balance the time of possession. Subsequently, they can accomplish this by stopping Taylor and pressing Ryan all over the field. 

Why The Colts Could Cover The Spread

The Colts are in disarray and playing through multiple injuries at the moment. Consequently, it has led to uninspired performances. Star receiver Michael Pittman logged a limited practice on Thursday and is considered “questionable” to play this week. However, he has yet to log a snap this season, and it will be difficult for him to come out of the gate firing. 

Ryan has faced the Chiefs four times in his career, producing a 2-2 record. Significantly, he last faced them on December 27, 2020, as a member of the Atlanta Falcons. In that game, Ryan completed 27 of his 35 passes for 300 yards, two touchdowns, and no interceptions. Taylor has never faced the Chiefs and will get his first crack at them. 

The Colts have a flurry of injuries and must find a way to overcome them. Likewise, their defense must step up. DeForest Buckner is the top pass rusher but has not yet recorded a sack. However, there may be some hope coming. Darius Leonard logged a limited practice and could return this Sunday. Significantly, the Colts have missed his prescience as teams have gutted the defense across the middle. 

The Colts will cover the spread if Taylor can pound the rock and work the clock, keeping Mahomes off the field. Additionally, Ryan must perform better. He has disappointed many so far and must improve. 

Final Chiefs-Colts Prediction & Pick

The Colts might have a chance if this game were later in the season. However, it is September, and the Colts are hurting. The Chiefs are on fire, and their offense will continue to fire on all cylinders. Expect the Chiefs to cover the spread and rout the Colts. 

Final Chiefs-Colts Prediction & Pick: Kansas City: -5.5 (-110)