The Panthers' tenth win took them nine points clear of the Giants, and earned them their first title in over 50 years.
Belfast Giants have now lost two straight.
Noah Clarke gave Belfast the lead on a penalty, but the Panthers responded almost instantly with a powerplay goal from Bruce Graham.
Kevin Saurette restored Belfast's lead early in the second, but again the Panthers hit back through David Clarke.
David Ling put Nottingham ahead for the first time, only for Adam Keefe to make it 3-3, but the Panthers' title celebrations were triggered thanks to late goals from Pat Galivan and Matt Francis.
A 500-strong travelling contingent were at the Odyssey Arena to celebrate the Panthers' victory.
The two sides take to the ice at the same venue on Saturday for a second clash at 7pm.