Chris Cardona has resigned as deputy leader of the Labour party, Robert Abela told reporters outside Castille on Wednesday.
Cardona had been under pressure to go after he was named in court in connection with the murder of Daphne Caruana Galizia.
The prime minister said he was informed that a resignation letter had been sent to the party.
The PL in a statement later confirmed the resignation and thanked Cardona for his service and loyalty.
Abela said the process to elect a new deputy leader has already started, with an extraordinary general meeting to be held in the second week of July.
Cardona has so far remained silent on the issue of his resignation, which marks the end of a 24 year political career.
The criminal lawyer had been under pressure to step down after he was named in court in connection with the murder of Daphne Caruana Galizia.
The self-confessed murder middleman, Melvin Theuma, claimed Cardona had used a friend to pay one of the hitmen 350,000 euro.
He also claimed the economy minister was secretly taken to a Sliema hospital after an attempted overdose.
The former economy minister denied all involvement in the October 2017 killing during an extensive interview with Times of Malta earlier this month.
Cardona had stepped down as MP in April but remained as deputy leader of the Labour party.
However on Tuesday, Abela said that he had asked his deputy to resign.