Dr Imran Farooq, a leader of Karachi's influential MQM party, was stabbed to death near his home in Edgware, north London in September 2010.
Khalid Shamim and Mohsin Ali were detained near the Pakistan-Afghanistan border in Chaman, Balochistan province.
They are to be handed to Pakistan's Federal Investigation Agency.
The BBC's Shahzeb Jillani in Pakistan says the murder was widely seen as a politically-motivated killing because Dr Farooq was reportedly planning to break away from the MQM leadership in London and start a new party.
The arrested suspects and a third man named Mohammed Kashif Khan Kamran worked for the MQM party, officials said.
In a statement, the MQM party denied any association with the suspects or involvement in the murder of Dr Farooq and accused the Pakistani government of political victimisation.
Dr Farooq was parliamentary leader in the Pakistani National Assembly when he went into hiding during a military operation against the MQM (Muttahida Quami Movement party) in 1992.

George Wharton, 14, and Rhy Baker, 13, died when Thomas McMeekin crashed into a tree in Morley, near Leeds, on 7 March.
The defendant and a teenage passenger were also left paralysed by the crash, Leeds Crown Court was told.
McMeekin, of Bruntcliffe Road, Morley, pleaded guilty to dangerous driving.
One witness told the hearing McMeekin had driven "like a lunatic".
He was accused of "showing off" while driving the car, which had been bought for him by his mother just five days before the crash.
The court heard he had advertised "lifts cheaper than taxis" on social media.
He will be sentenced next month.

Officials from Cuba and Norway, the two countries brokering the peace process, said a week of discussions would begin in Havana on 10 December.
Colombia's president stopped the talks after the rebels seized Gen Ruben Dario Alzate and two others on 16 November.
The captives were released on Sunday.
They were handed over to a humanitarian mission led by the International Red Cross and taken to a military base near the city of Medellin before travelling to be reunited with their families.
"We consider the crisis over and announce that we have agreed that the next cycle of conversations will take place between 10 and 17 December," Reuters quoted a joint statement read by a Cuban official as saying.
The negotiators said the next round of talks would focus on a de-escalation of the conflict, and on meeting the relatives of victims.
They also said the parties had agreed to establish a permanent system to deal with any future crises.
They will reconvene around mid-January, on a date not yet determined.
The negotiations have been under way in Havana since November 2012 and aim to bring an end to five decades of conflict, in which 220,000 people are estimated to have died.
The Red Cross and the Farc said that the handover on Sunday had taken place in a remote location in Choco province, an isolated jungle region on Colombia's Pacific Coast.
Gen Alzate, Cpl Jorge Rodriguez and lawyer Gloria Urrego had been kidnapped 14 days earlier while travelling along the Atrato river by boat. They had ventured into territory dominated by the Farc in civilian clothes and without a security detail.
The Farc said they kidnapped the general because they were unhappy that President Juan Manuel Santos had continued military operations against them during peace talks.
The left-wing rebel group has renewed calls for both sides to call a ceasefire while the peace negotiations proceed.
The government has rejected such calls, saying that a truce would only help the rebel group regroup and rearm.
Gen Alzate resigned from his post on Monday, saying he should have taken more security precautions.

The animals were happily munching in the front garden of a house in Drummond Road close to its junction with the busier Culduthel Road.
Police received calls from members of the public who were both concerned for the sheep and seeking to reunite the animals with their owner.
Officers helped to have the sheep rounded up and returned to their home.
It is understood the animals are kept locally.
Pakistan authorities have detained two men suspected of being involved in the killing of an exiled politician in London five years ago, officials say.
[NEXT_CONCEPT]
A motorist was driving "like a lunatic" when he caused a crash which killed two teenage passengers and severely injured two others, a court heard.
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The Colombian government and Farc rebels have agreed to resume peace talks, which were suspended last month over the abduction of an army general, mediators say.
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Police have been called to deal with a small flock of sheep loose near Inverness city centre.