Jonathan Doerer made a 41-yard field goal in overtime for the Irish to leave Doak-Campbell Stadium 1-0.
FSU kicker Ryan Fitzgerald made a 50-yard attempt in the overtime period, but it was negated because head coach Mike Norvell called a timeout to challenge a fumble on the previous play. After a review, officials agreed Milton's arm was moving forward and it was an incomplete pass. Fitzgerald's second attempt in overtime, a 37-yarder, sailed wide left, giving Notre Dame to set up Doerer for the game-winner.
Jordan Travis, who beat out Milton -- a UCF graduate transfer -- for the FSU starting job, started the Seminoles' comeback with an eight-yard touchdown to Andrew Parchment.
Milton, who hadn't played since a leg injury in November 2018, entered the game with nine minutes remaining in the fourth quarter. He connected on three passes then Treshaun Ward capped the drive with a two-yard score to make it 38-35.
The Irish went three-and-out on the ensuing drive. Milton then led FSU on a 10-play, 46-yard drive that ended with Fitzgerald's game-tying 43-yard field goal with 40 seconds left.
Jack Coan, a Wisconsin graduate transfer, was 26 of 35 for 366 yards and four touchdowns in his Notre Dame debut. He threw TD passes to tight end Michael Mayer, running back Kyren Williams, and wide receivers Kevin Austin and Joe Wilkins.
Coan hit Mayer for a 41-yard score on a fourth-and-one at the FSU 41 on the opening drive. FSU tied it 7-7 when Jashuan Corbin broke free on an 89-yard run at 5:06 of the first.
Travis gave FSU its first lead with a two-yard run then Coan engineered a 10-play drive that ended with Doerer's 48-yard kick.
All-American safety Kyle Hamilton made the first of his two interceptions on the night against Travis to set up Coan's 23-yard TD to Wilkins for a 17-14 halftime lead.
On the third play of the second half, Ja'Khi Douglas beat Houston Griffith down the left sideline to catch a 60-yard TD pass from Travis. But Coan regained the lead, 24-20, for the Irish with a 37-yard heave to Austin.
Hamilton darted from the left hash to the opposite sideline to make his second interception on FSU's next drive. The Irish again capitalized on the turnover with Williams' six-yard TD to cap a seven-play, 69-yard drive for a 31-20 lead.
Travis was picked off for a third time, this time by Clarence Lewis, which led to Chris Tyree's one-yard score for a 38-20 lead with 4:37 to go in the third.
Notre Dame struggled to run the ball, rushing for only 65 yards on 35 attempts. Irish offensive coordinator Tommy Reese leaned on Coan's efficiency in the passing game throughout the contest. Coan isn't as mobile as his predecessor Ian Book, but he displayed command of the offense.
Defensive coordinator Marcus Freeman's defense made three interceptions in his Irish debut. Hamilton had two and Lewis had the other one. Linebacker JD Bertrand and defensive lineman Isaiah Foskey played well up front. Bertrand had 11 tackles, including six solo, while Fosky had two sacks, eight tackles (five solo), and two tackles for loss.
Williams didn't make a difference as the Irish's punt returner with only one return for four yards. Doerer made both of his field goals and all five of his extra-point attempts. Punter Jay Bramblett had five punts, including a long of 50 yards, for 236 yards.