Florida State's win coupled with North Carolina State's loss to North Carolina puts the Seminoles back in control of the Atlantic Coast Conference's Atlantic Division while Duke (6-3, 3-2) dropped out of the undisputed lead in the league's muddled Coastal Division.
Florida State (8-1, 5-1) rolled up 560 yards in offense while limiting Duke to 232.
Duke quarterback Sean Renfree completed 13 of 21 passes for 92 yards before being knocked out of the game in the second quarter with an unspecified head injury. Anthony Boone was 3 of 15 for 37 yards against a Florida State defense that leads the ACC in virtually all categories.
Duke coach David Cutcliffe said after the game that Renfree would be further evaluated by medical personnel, but still wasn't feeling very good after the game.
Florida State, which has an open date before returning to action Nov. 8 at Virginia Tech, is unbeaten in 18 games against Duke and has won by 19 or more points in each of those games. It became clearly quickly Saturday that things weren't going to change.
The Seminoles scored on their third play of the game when Manuel hit Rashad Greene in stride for a 71-yard touchdown and didn't let up, racing to a 31-0 lead just four minutes into the second quarter.
But after adding two quick touchdowns in the first five minutes of the third quarter to take a 45-7 lead on Manuel's 35-yard scoring pass to Kelvin Benjamin, Florida State bogged down with mistakes and managed just Hopkins' record-breaking field goal in the final 25 minutes.
Hopkins had appeared to have broken the conference record for career field goals held by former Maryland kicker Nick Novak with a 51-yarder, but Florida State was whistled for delay of game and he then drilled his career best with ease for the new mark of 81. He is six shy of former Georgia kicker Billy Bennett's NCAA mark of 87.
Freeman, who finished with 105 yards rushing, scored on runs of 9 and 14 yards and James Wilder Jr. chipped in with 70 yards and a 1-yard TD run. The two sophomores have taken over for leading rusher, Chris Thompson, who suffered a season-ending knee injury in last week's 33-20 win at Miami.
Duke's Conner Vernon caught three passes to extend his nation's best string to 44 consecutive games with at least one catch.
North Carolina State (5-3, 2-2) had previously controlled its destiny in the Atlantic Division on the strength of a 17-16 win over the Seminoles earlier, but lost the advantage with a 42-35 loss Saturday at North Carolina.