The men set the building on fire over a non-payment of extortion money, the court said.
The 2012 blaze killed over 260 workers, who could not escape because the doors were locked.
A garment factory fire which claimed more than 260 lives in Pakistan in 2012 was a case of arson and not an accident, the Anti-Terrorism Court in Karachi ruled on Tuesday. The presiding judge sentenced two men to death for their involvement.
The men, who were previously affiliated with a political party currently part of the ruling coalition, were found guilty of setting the building on fire because of a non-payment of extortion money by the owners of the factory.
The fire at the Ali Enterprises building in southern Karachi spurred widespread calls to improve working conditions for garment laborers, after people were trapped in the factory because the building's doors were locked.
Of the eight other people accused in the case, four were found complicit while the other four were acquitted, including the then-provincial minister for industries, defense counsel Abid Zaman told reporters outside the court.
As many as 400 witnesses gave statements in 171 hearings over the course of eight years.
Ties to Movement-Pakistan
The two men who were handed the death sentence, Rehman Bhola and Zubair Chariya, were both members of the Movement-Pakistan (MQM-P) party, a group linked to violence in Karachi.
The party is also a partner in Prime Minister Imran Khan's coalition government.
The current MQM leadership has denied any involvement with the fire and says that the blaze was directed from abroad, where several of the party's leaders live, including MQM's founder Altaf Hussain, who lives in exile and is now a British citizen.
MQM-Pakistan leader Faisal Subzwari in a tweet quoted a spokesperson for his party as saying that the acquittal of Rauf Siddiqui, the former industries minister "proves that MQM-Pakistan has nothing to do with this case."
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