Monday night's match saw two of the league's hottest talents go toe-to-toe with Mahomes taking on Ravens quarterback Lamar Jackson.
And it was the Ravens who got on the board first, with Justin Tucker true with the boot from 26 yards as Baltimore took a 3-0 lead.
But the reigning Super Bowl champions were not down for long as Mahomes, who had 385 yards in the air, rushed for a score less than three minutes later.
He then went on to score three touchdowns in the second quarter – including a 49-yard pass to Mecole Hardman as the Chiefs went into the break 27-10 up.
Another field goal for Tucker brought the game to within two scores, but Mahomes drove the Chiefs to the end zone again in the fourth, a two-yard pass to Eric Fisher sealing the win and a 3-0 record to start the season.