Chiefs quarterback Mahomes went 23 of 35 for 294 passing yards and three touchdowns at Arrowhead Stadium, while also rushing for an incredible 27-yard score at the end of the first half.
The reigning NFL MVP became the first player in Chiefs franchise history to record multiple passing touchdowns and a rushing touchdown in a postseason game.
Tyreek Hill had two receiving touchdowns and Sammy Watkins found the end zone off a 60-yard reception from Mahomes to end the Titans' impressive playoff run, which included victories over the New England Patriots and Baltimore Ravens.
Running back Derrick Henry started positively with a four-yard rushing touchdown for Tennessee, but Hill hit 21.27 miles per hour off an eight-yard reception to reduce the arrears.
After a string of penalties from the Chiefs defense, Titans quarterback Ryan Tannehill found Dennis Kelly with a one-yard touchdown pass at the end of a 15-play, 75-yard drive that lasted nine minutes and seven seconds to restore his team's 10-point advantage – the 321-pound offensive lineman becoming the heaviest player with a receiving TD in postseason history.
Hill crossed for a 20-yard receiving touchdown before Mahomes took matters into his own hands with a stunning solo score 11 seconds before half-time, sending the Chiefs into the interval with a 21-17 lead.
Kansas City's defense frustrated the Titans in the third quarter and Damien Williams made it seven touchdowns in four postseason games as a Chief when he finished over the ground from three yards at the start of the final period.
Mahomes' stunning pass to Watkins put the Chiefs 18 points clear and a 22-yard touchdown reception for Anthony Firkser after pulling off a fake punt proved to be solely a consolation for the Titans.