Fenech, 38, was taken to court under a heavy armed police escort nearly two years to the day since three men were charged with having set off the bomb that killed the journalist on October 16, 2017.
Caruana Galizia's reporting was continued by the Daphne Project, determined to root out wrongdoing in Malta, which is a financial haven for many business figures from overseas. The case has developed into a political crisis for the government of Prime Minister Joseph Muscat.
Official sources say he could resign on Sunday (December 1).
Outside court Ms Caruana Galizia's family said it was now time for Mr Muscat to resign as the allegations of shady dealing stretch to those around him.
Asked about this before Fenech was charged, a spokesman for the prime minister said that Muscat "has pledged various times he wants to see this case through. He will make announcements in due course".
Sources briefed on the murder investigation told Reuters that police regard Fenech as the mastermind of the journalist's killing.
Ms Vella also called for Mr Muscat and his former chief of staff, Keith Schembri, to be "properly investigated" for their "possible involvement in Daphne's assassination".
The November 20 arrest of Yorgen Fenech, who had direct ties to Muscat's cabinet, led to widespread calls for resignation.
He will step down once his Labour Party has chosen a new leader, said the party insiders.
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His chief aide, Keith Schembri, quit this week amid reports he was being questioned by police, while Tourism Minister Konrad Mizzi also resigned and Economy Minister Chris Cardona took the decision to suspend himself.
Muscat said on Thursday the government had turned down the pardon request on the advice of the attorney general and the police.
Neither Schembri or his lawyers have commented since his resignation or arrest. They had been accused by Caruana Galizia of being involved in corruption, which they denied.
Mizzi on Tuesday denied any business links with Fenech and any wrongdoing.
Mr Fenech was identified previous year as being the owner of a mysterious Dubai-registered company, 17 Black, listed in the Panama Papers - a massive leak of documents from an offshore law firm in 2016.
Previous year he was identified as the owner of a Dubai-registered company called 17 Black, which is listed in the Panama Papers, a collection of leaked confidential documents showing how wealthy and powerful companies around the world use tax havens to get around the law.
There is no evidence that funds were ever transferred to Mizzi and Schembri, and Mizzi has denied any connection with 17 Black or the murder.
Investigators subsequently told a court that the bomb was set off from a yacht off Valletta harbor.
The arrest comes as the long-stalled investigation into the October 2017 auto bomb murder of Caruana Galizia intensifies.