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Sammy Watkins had a strong start to the game as he collected a deep pass from Tyrod Taylor to take his team into Chiefs' territory, and Dan Carpenter put the Bills ahead by slotting a 27-yard field goal through the posts.
Watkins continued his domination in the first quarter when he raided past Sean Smith to haul in another deep strike from Taylor to find the endzone from 28 yards.
Watkins scored his second touchdown of the match by going deep down the sideline and grabbing the ball over Smith to put the Bills into a nine-point lead after Carpenter's kick for the extra point sailed wide of the posts.
However, the Smith-Maclin combination was to bring Kansas City back into the game as the wideout beat man coverage down the sideline to record a 41-yard touchdown.
Cairo Santos saw his field goal hit the bar before the break to deny the home side the lead, but they did go in front early in the third quarter when Smith fired the ball into the endzone for Travis Kelce to catch above his head.
The Chiefs extended their lead to eight points through a 49-yard field goal from Santos, but Buffalo hit back when LeSean McCoy found the endzone from close range after collecting a short pass from Taylor. However, their two-point conversion failed to leave the hosts narrowly ahead.
Andy Reid's men edged further ahead through the boot of Santos as he nailed his kick from 38 yards as the Chiefs' offense took valuable time of the clock.
Taylor was unable to inspire the visitors into a response and Smith put the game beyond the reach of the AFC East outfit by taking his team into field-goal range, and Santos delivered once again to hand the Chiefs an eight-point lead.
Taylor had time to launch a drive to tie the match, but he was denied by the home side's defense as Reid's team held out for the win.
The result leaves Kansas City at 6-5 in their season, while the Bills drop to 5-6.