Mahomes, broke the single-season record for total yards, surpassing Drew Brees' previous record with 5,614 yards in a season where he led the league in touchdown passes with 41.
The quarterback led his team to first seed in the AFC with a 14-3 record and then battled through an ankle injury to take the Chiefs back to the Super Bowl for the third time in four seasons.
Mahomes, who also was MVP in 2018, was named MVP at the NFL Honours event at the Phoenix Convention Center.
In a video message, he thanked his family and the Chiefs organisation and his teammates before making clear his focus was on Sunday's big game.
"Every day we are giving everything we have together to go for the ultimate goal - the Super Bowl. Let's continue to go for that dream this weekend," he said.
New York Giants head coach Brian Daboll (47) won the Coach of the Year award after leading the team to their first post-season campaign since 2016 in his first year in charge.
San Francisco 49ers defensive end Nick Bosa (25) was voted Defensive Player of the Year and Minnesota Vikings wide-receiver Justin Jefferson (23) was named Offensive Player of the Year.
Seattle Seahawks quarterback Geno Smith (32) was named the NFL Comeback Player of the Year after he enjoyed a strong season, seven years after he was last a regular starter.
Former New York Jet Smith completed a league-best 69.8% of his passes and threw for a career-high 4,282 yards and 30 touchdowns.
Damar Hamlin (24), the Buffalo Bills safety who suffered a cardiac arrest during the penultimate week of the regular season before recovering attended the event and received a standing ovation after a powerful speech.
