Coming off a seven-point win in Tampa, the Lions (2-0) opened their home portion of the season with their largest margin of victory in club history, breaking the record the club set in 1995 with a 44-0 win over Jacksonville.
The revamped Lions have started a season with two straight wins since taking the first two games of a 2007 campaign that saw the team go 6-2 to start the first half, only to finish it with a mark of 7-9.
"We can still play better, we didn't start the game very well," said Detroit head coach Jim Schwartz. "Won by, obviously, a wide margin and started playing better as the game went on, particularly when we started getting into that second quarter, third quarter, got some turnovers, started capitalizing on some opportunities on offense, putting points on the board."
Stafford, who threw three scores last week, was efficient again as he went 23- for-39 with 294 yards and an interception and was helped by a defense that caused six turnovers, including takeaways on three straight KC possessions in the third and fourth quarters.
"I think we played good as an offense," said Stafford. "Our defense played unbelievable, got turnovers, not only stops, but turnovers. When we get the ball at short field like that, when they're getting huge momentum swings we're able to put points on the board after them. It was fun to be a part of."
Calvin Johnson had two touchdown catches for the second straight week while Jahvid Best had a score through the air and on the ground as Detroit won its sixth straight game dating back to last season.
Meanwhile, the Chiefs (0-2) have been outscored by a margin of 89-10 in its first two games of the season and lost running back Jamaal Charles early in the game to a left knee injury that saw him carted off the field.
Matt Cassel had a rough day as well as he went just 15-for-22 for 133 yards with three interceptions and a lost fumble for Kansas City, which has lost four in a row including a playoff loss to Baltimore last season.
"This whole game came down to turnovers, it's what killed us today," said Cassel. "I have to do better taking care of the ball, we have to do better taking care of the ball because it will help us on drives and put us in a better position to win."
Kansas City last started a season 0-2 in 2009, when the team lost its first five games before finishing 4-12.
Detroit started the game with the ball and used the opening drive to take a 7-0 lead when Stafford hit Johnson on a 15-yard score 4:10 into the game. The drive saw Kansas City pick off Stafford, but it was fumbled and Detroit recovered. Consecutive personal foul calls on the Chiefs preceded the touchdown by Johnson.
Kansas City responded with a pounding drive that saw the team rush six straight times for 65 yards before stalling at the Detroit 15. A 33-yard field goal from Ryan Succop made it a 7-3 game with eight minutes left in the first.
A three-and-out from Detroit saw Kansas City get the ball back at the 33 and mostly use the run again to get into field goal position, but Succop was wide to the left on a 44-yard attempt.
Detroit pinned Kansas City deep in its territory off a punt and held the team to a three-and-out.
The Lions then had a short field to work with as they began their possession at the Kansas City 45. Two plays later, Stafford hit Tony Scheffler over the middle inside the 10 and the big tight end took it in from 36 yards out for a 14-3 lead with 5:50 to play in the second.
A 45-yard grab by Dwayne Bowe got Kansas City into Detroit territory. Three plays later, though, Bowe had a pass slip through his fingers and it was intercepted by Chris Houston, who took the ball back to near midfield.
Detroit only made it to the Kansas City 33 and got three points on a 51-yard boot by Jason Hanson for a 17-3 lead with 67 seconds to play in the half.
Cassel was again a victim of his own receivers as Jerheme Urban had an easy pass slip through his fingers and Amari Spievey came up with the pick. That led to a 28-yard field goal from Hanson to give the Lions a 17-point lead at the break.
On its second touch of the third quarter, the Lions were able to add to their lead. The 10-play, 84-yard drive was capped on a 4th-and-goal play at the one- yard line when Stafford hit Johnson in the end zone for a 27-3 lead with 1:17 left in the frame. The score was setup on a 35-yard catch-and-run from Best for a first down at the Kansas City six-yard line.
Cassel was sacked on the first play of the Chiefs' next possession and fumbled the ball, which Detroit recovered at the KC 23. On the first play of the fourth quarter, Best took the ball into the endzone on a nine-yard catch for a 34-3 lead.
Another fumble, this one from Dexter McCluster saw Detroit get the ball back at the Kansas City 18 with Best diving over the pile from a yard out for a 41-3 lead with 11:31 to play.