Melbourne have claimed an thrilling two-point upset win over reigning premiers Brisbane and crashed Lachie Neale's 300th game celebrations in the process.

The Lions led by 17 late in the second term and threatened to break the game wide open before the Demons kicked five consecutive goals in the third quarter to set up a show-stopping finish.

Melbourne took the lead in the fourth, then withstood a late Lions surge to claim a memorable 16.8 (104) to 15.12 (102) win at the MCG, their best victory under new coach Steven King to date.

It condemned Neale and 200-gamer Josh Dunkley to defeat in their milestone games.

Lions utility Jarrod Berry suffered a calf injury in the second quarter and Bruce Reville limped off in the fourth.

Melbourne's Harrison Petty was helped off by trainers at the end of the third term after he appeared shaky and unsteady on his feet.

The club later confirmed he had suffered a head injury, indicating it could be a delayed onset concussion.

Second-year Demons midfielder Harvey Langford (27 disposals, three goals) was wonderful along with the magnificent Kade Chandler (17 disposals, three goals), who sank two huge final-quarter goals.

Max Gawn (seven clearances, 23 hitouts, 21 disposals) got the better of Sam Draper (23 hitouts).

Lions co-captain Harris Andrews (22 disposals, 12 marks) was masterful down back, though opponent Jacob van Rooyen (three goals) jagged two crucial final-quarter goals.

Neale (31 disposals, 10 clearances), Darcy Wilmot (27) and Reville were busy for Brisbane.

In his 50th game, Logan Morris dobbed three goals along with Charlie Cameron, while Cam Rayner kicked two.

Kysaiah Pickett could be looked at after Brisbane's Noah Answerth required a concussion assessment following a bump from the star Demon.

Lions ruckman Darcy Fort was a late withdrawal through illness, with Zane Zakostelsky recalled.

Scores were level at quarter-time but the Lions seized control in the second term and led by 16 at halftime.

The Demons were celebrating 'Jim's Game', commemorating late Irish club legend Jim Stynes, and had a violinist and Irish dance troupe performing a jig after every Melbourne goal.

That violin kicked into overdrive as Melbourne kicked five goals on the spin in the third term to regain the lead.

The Demons led by six points at the final change but when Hugh McCluggage put Brisbane back in front, the Lions appeared set to go on with it.

But van Rooyen took a huge mark over Andrews to restore Melbourne's lead before Chandler sent the MCG into ecstasy.

The Lions mounted a late comeback and Rayner had the chance to put Brisbane back in front but missed, before Melbourne held on.

Brisbane next host Adelaide at the Gabba on Sunday while Melbourne play Richmond at the MCG on Friday night.