The country is already grappling with a depressed economy, the after-effects of devastating floods that hit 21 million people in mid-2010.
The Muttahida Qaumi Movement (MQM) made the announcement Sunday, days after its two federal cabinet ministers resigned, abandoning crisis talks with the main ruling Pakistan People's Party that had scrambled to keep them on board.
An administration that took power less than three years ago following elections has now lost its majority in parliament and faces possible collapse if the opposition unites to pass a vote of no-confidence.
Prime Minister Yousuf Raza Gilani tried to appear calm on live television, telling journalists: "The government is not going to fall."
"I was unanimously elected, all parties voted for me in the national assembly. We have contacts with all parties," Gilani said, indicating that behind-the-scenes talks to shore up a new coalition were already under way.
Without MQM's 25 seats, the PPP's coalition numbers 160 seats in the 342-member national assembly, 12 short of the 172 required for a majority.
All eyes will now turn to Pakistan's main opposition party, the Pakistan Muslim League Nawaz (PML-N) led by former prime minister Nawaz Sharif, which would need to support any possible parliamentary vote of no-confidence.
But political analyst Hasan Askari doubted any immediate prospect of a no-confidence vote, saying that Sharif appeared unwilling to bring down the government immediately and face responsibility for the country's myriad crises.
Troubled relations between Sharif's party and the MQM gives the government breathing space of at least three to four weeks to stitch together a new majority, analysts said.
"The government will try to win over small groups so you'll see lots of politicking," said Askari.
One of those parties set to be wooed could be Jamiat Ulema-e-Islam Fazl (JUIF), the country's most prominent religious party that took seven lawmakers out of government on December 14 after Gilani sacked one of its ministers.
MQM has long been at odds with unpopular President Asif Ali Zardari's PPP over political violence in Karachi, tax reforms demanded by the International Monetary Fund, corruption and crippling inflation.
"We have expressed no confidence against anti-people policies," MQM's Faisal Sabzwari told reporters.
"The government should immediately roll back the increase (of nine percent) in petroleum prices and prices in general and take steps to eliminate corruption," he said.
An MQM statement said the government was "crushing the people".
"We'll support the government's positive steps while sitting in the opposition and will openly oppose the anti-people decisions," the statement said.
MQM remains in the coalition in the southern province of Sindh, of which Pakistan's largest city of Karachi is the capital.
MQM's Farooq Sattar, minister for overseas Pakistanis, and ports and shipping minister Babar Ghauri, last week submitted their resignations, but the party had stopped short of joining the opposition.
PPP luminaries had appeared publicly confident of sealing a deal to keep MQM on board, but analysts say that the party had decided it no longer wanted to be implicated in an increasingly unpopular government.