LONDON -- When Alex Smith had no options left, he ran. And he ran far.
The Kansas City quarterback carried the ball five times and gained 78 yards, including a career-high 49-yard scramble in the second quarter that set up his 12-yard touchdown run.
With a comfortable lead in hand, Smith settled into his usual role, throwing for 145 yards and a pair of touchdowns to lead the Chiefs to a 45-10 victory over the Detroit Lions at Wembley Stadium in the last of three regular-season NFL games in London.
"We got a lot of guys with a lot of different strengths," Smith said. "We can present a lot to a defense. It's hard for them to defend."
De'Anthony Thomas, Charcandrick West and Spencer Ware also rushed for touchdowns -- the first time the Chiefs had four different players rush for scores in the same game since 1960. Thomas ended up with 100 total yards, while West ran for 97. Travis Kelce and Jeremy Maclin caught the two TD passes in the second half.
"Alex was putting the ball on the money today and Charcandrick was running north," said Kelce, who had six receptions for 49 yards.
The Chiefs (3-5) were at Wembley for the first time, while the Lions (1-7) played in London for the second straight season.
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.
"Not a good outing, obviously. An understatement," Lions coach Jim Caldwell said. "We ran the ball decently early on, but we reached the point where we wouldn't be able to regain lost ground quickly enough to keep running."
The Kansas City pass rush posed huge problems for the Lions, 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 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.
"He had some very positive yards for us at needed times," Chiefs coach Andy Reid said. "We know he can run. We don't really want him to run, but if it works out that way that's OK."
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 scored from 17 yards right after Thomas returned a punt 37 yards to the 16.
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 Caldwell, who fired Lombardi after last week's 28-19 loss to the Minnesota Vikings.
"Jim Bob called a good game," Stafford said, "but we just failed to execute."