Mahomes is thought to be slight favourite to be named this season's Most Valuable Player, just ahead of Jalen Hurts, who set the record for most rushing touchdowns by a quarterback in one season - 15 - as Philadelphia denied Brock Purdy a fairytale Super Bowl appearance.
Purdy was this season's 'Mr Irrelevant', the nickname given to the last man selected in the draft, yet was thrust into the limelight in December after injuries to Trey Lance and Jimmy Garoppolo.
The 23-year-old led the 49ers to victory on his first seven NFL starts and hoped to become the first rookie quarterback to reach the Super Bowl, but both he and his back-up Josh Johnson were injured as the Eagles' pass rush proved too strong.
Miles Sanders had already got into the end zone for the hosts before Purdy injured his right elbow as he was sacked for a fumble by linebacker Haason Reddick.
Now led by 36-year-old journeyman Johnson, the 49ers managed to draw level midway through the second quarter after Christian McCaffrey crashed through for a 23-yard touchdown.
But any hope of San Francisco reaching the Super Bowl despite playing their fourth-choice quarterback was dashed on the next three possessions.
Sanders got in from 13 yards before Reddick got the ball straight back with a fumble recovery and Boston Scott ran in a 10-yard touchdown to make it 21-7 right on half-time.
San Francisco had other injury concerns before Johnson was also forced to the sideline after being tackled mid-throw on their first possession of the second half.
Purdy was able to return, with his arm heavily strapped, but was unable to throw properly and the 49ers let their frustration show by giving away a host of penalties, allowing Hurts to cap a 91-yard drive before Philly added a field goal.
That means the Eagles will play in the Super Bowl for the fourth time and the first time since 2018, when they beat the New England Patriots to claim their first NFL championship.
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