The independent Electoral Boundaries Commission on Thursday announced nine existing electoral districts across the state will be replaced, including Mr Pakula's seat of Keysborough.
His constituents will be split between the remaining seats of Clarinda, Dandenong, Mordialloc and Mulgrave.
"So what the hell happened to Keysborough?" Mr Pakula tweeted following the announcement.
Mr Pakula is the state minister for major events, trade, tourism, racing and sport.
He was first elected as a member of the upper house for the Western Metropolitan region in 2006, before moving to the lower house as the member for Lyndhurst in a 2013 by-election.
The seat was replaced by Keysborough before the 2014 election, which Mr Pakula retained.
Former attorney-general Jill Hennessy's seat of Altona has been abolished and largely replaced by Point Cook, which will take in parts of Werribee to reflect population changes.
The eastern seats Burwood (Labor), Ferntree Gully (Liberal), Forest Hill (Liberal) and Mount Waverley (Labor) have all been abolished and replaced with the new seats of Ashwood and Glen Waverley.
New seats include Kalkallo in Melbourne's north, Laverton in the west and Pakenham in the southeast, all likely to be won by Labor.
Electoral boundary changes will help the Greens retain Brunswick and improve their chances in Footscray.
In regional Victoria, the electoral district of Buninyong is largely replaced by Eureka, while the seat of Ripon changes significantly, losing the towns of Charlton, Donald and Stawell and taking in more of Ballarat.
Ripon is held by Liberal MP Louise Staley by just 15 votes.
There are also significant boundary changes around Geelong and the Surf Coast.
More than 900,000 people - or 21.28 per cent of the total number of voters - will be transferred to different districts, which will take effect at the next state election in November 2022.
The boundaries of the electoral regions, which affect upper house seats, have also changed, with the Eastern Metropolitan Region renamed North-Eastern Metropolitan.
The number of electors moved to different regions is 714,569, or 16.7 per cent of total voters.
CHANGES TO VICTORIA'S ELECTORATES
Abolished:
* Altona (Labor, Jill Hennessy)
* Buninyong (Labor, Michaela Settle)
* Burwood (Labor, Will Fowles)
* Ferntree Gully (Liberal, Nick Wakeling)
* Forest Hill (Liberal, Neil Angus)
* Gembrook (Liberal, Brad Battin)
* Keysborough (Labor, Martin Pakula)
* Mount Waverley (Labor, Matt Fregon)
* Yuroke (Labor, Ros Spence)
New:
* Ashwood
* Berwick
* Eureka
* Glen Waverley
* Greenvale
* Kalkallo
* Laverton
* Pakenham
* Point Cook