LONDON -- Whenever the Chiefs needed to pick up some yards, Alex Smith ran for them.

The Kansas City quarterback threw for 145 yards and two touchdowns, and ran for 78 yards and another TD to lead Kansas City over the Detroit Lions 45-10 Sunday at Wembley Stadium.

Smith scrambled his way through the Detroit defense for some big plays, including a career-high 49-yard run in the second quarter that set up his 12-yard touchdown run.

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The Chiefs (3-5) were at Wembley for the first time, while the Lions (1-7) played in London for the second straight season.

De'Anthony Thomas, Charcandrick West and Spencer Ware also rushed for touchdowns for the Chiefs. Thomas ended up with 100 total yards, while West ran for 97. Travis Kelce and Jeremy Maclin caught TD passes in the second half.

The Lions were playing for the first time since offensive coordinator Jim Bob Cooter took over for the fired Joe Lombardi. And although the offense got moving on the opening possession, it stalled horribly after that.

Matthew Stafford threw for 217 yards, one touchdown and two interceptions. Also, Calvin Johnson had 85 receiving yards, while Joique Bell ran for 56. But after the Lions took a 3-0 lead on 35-yard field goal from Matt Prater, Detroit was hapless with the ball.

The Kansas City pass rush posed huge problems, and Stafford's two interceptions resulted in 10 points going the other way. He was sacked six times, including on fourth-and-8 near midfield early in the fourth quarter while trailing 31-3.

Smith also got tackled a few times, mainly because he was running effectively the ball and picking up some key yardage. The quarterback helped set up the first touchdown by scrambling 8 yards for a first down. On the next play, Thomas ran in from the 10.

At the start of the second quarter, Smith ran for a career-high 49 yards to open a drive. On third-and-10 from the 12, Smith scrambled into the left corner to make it 14-3.

On the defensive side, Sean Smith and Justin Houston both picked off passes from Stafford. Smith's interception resulted in a 33-yard field goal from Cairo Santos. Houston's pick set up West's 8-yard TD run up the middle.

Kelce caught a touchdown pass from the 2 at the start of the second half, and Maclin score from 17 yards right after Thomas returned a punt 37 yards to the 16.

With the game out reach, Stafford threw a 21-yard touchdown pass to Lance Moore. But Ware restored the 35-point lead with Chase Daniel in at quarterback by running in from the 4.

The Lions trailed by 21 points at the half, the same deficit they erased last year at Wembley by scoring 22 unanswered points against Atlanta. But Sunday's ineffective offense will lead to more questions for coach Jim Caldwell, who fired Lombardi after last week's 28-19 loss to the Minnesota Vikings.