The Spirit of Britain has left the Port of Dover, in Kent, as P&O Ferries resumed Dover-Calais sailings for freight customers on Tuesday evening.
The vessel was detained by the Maritime and Coastguard Agency (MCA) on April 12 after safety issues were found, but was cleared to sail last Friday.
The ferry company sacked nearly 800 seafarers with no notice on March 17, replacing them with cheaper agency workers. P&O Ferries has not operated between Dover and Calais since the mass sackings.
Passenger services are expected to resume early next week.
The Trade Unions Congress (TUC) has called for a public and commercial boycott of P&O Ferries.
The freight departure comes as P&O Ferries said on Tuesday night that a full investigation would be carried out after a vessel travelling between Cairnryan and Larne lost power off the Co Antrim coast.
The European Causeway, which can carry 410 passengers, was adrift five miles off the coast of Larne in the Irish Sea for more than an hour on Tuesday afternoon.
Earlier, the Marine Traffic website stated the vessel's automatic identification system status had been set to "not under command" which is reserved for use when a vessel is "unable to manoeuvre as required by these rules and is therefore unable to keep out of the way of another vessel".
A spokesperson for P&O Ferries said it had been a temporary issue and the European Causeway had travelled to Larne "under its own propulsion".
"There are no reported injuries on board and all the relevant authorities have been informed.
"Once in dock a full independent investigation will be undertaken."