Malawi's Supreme Court has ruled that the speaker of parliament can expel MPs who switch parties - a ruling which could bring down the government.
Mr Mutharika accused the UDF of blocking his fight against corruption
Most members of President Bingu wa Mutharika's party were elected on the ticket of the former ruling party.
Mr Mutharika also won elections for the United Democratic Front (UDF), before leaving to set up the Democratic Progressive Party (DPP).
More than 70 of the 193 MPs could be affected by the ruling.
About half of them are from the DPP, which has formed a minority government.
'Victory for democracy'
UDF supporters burst into song and dance at the packed courthouse as Chief Justice Leonard Unyolo made his ruling.
He said Section 65 of the constitution gave the speaker the power to expel MPs who switch parties.
The DPP had challenged this view.
Mr Mutharika (back) was chosen by his predecessor Bakili Muluzi (front) but the pair have since fallen out
"It's [a] victory for democracy," said lawyer Kalekeni Kaphale, who represented opposition political parties in the landmark case.
"This will help bring political sanity in the country as it will stop those in power from abusing their authority in poaching almost everyone they want to their side."
DPP Secretary-General Heatherwick Ntaba said he was confident that his party's MPs would be re-elected in by-elections.
Parliament is due to resume on 29 June to debate the budget.
However political analyst Rafiq Hajat told the BBC's Focus on Africa programme that it would take six months to organise so many by-elections, if the speaker does expel the MPs.
He said that in the meantime, the government would struggle to get the budget passed and so some interim measure such as a government of national unity would be needed.
Mr Mutharika left the UDF, accusing party officials of blocking his anti-corruption drive.