Eifert caught 44 passes for 624 yards and four touchdowns in a season in which the Fighting Irish went 12-0, earned the No. 1 ranking and a berth in the Bowl Championship Series title game.
Eifert owns the school records for career receptions (134) and receiving yards (1,779) by a tight end.
He is the first Notre Dame player to win the Mackey Award.
Other players under consideration by the John Mackey Award Selection Committee were Stanford Zach Ertz and Washington's Austin Seferian-Jenkins.
The award is administered by the Nassau County (N.Y.) Sports Commission. The John Mackey Award is named for the Hall of Fame tight end who played at Syracuse and for the Baltimore Colts and San Diego Chargers in the NFL.