Rene Meulensteen has replaced Martin Jol as Fulham manager after the Dutchman was sacked by the Premier League strugglers.
Defeat at West Ham United on Saturday was the club's fifth league defeat in a row which leaves them in the relegation zone after 13 matches.
Meulensteen, who was Sir Alex Ferguson's assistant at Manchester United for 12 years, was appointed as first-team coach in November but will now assume managerial duties - his first senior position.
"Rene Meulensteen was brought to Fulham to assist Martin and today was offered the challenge and opportunity to step in for Martin," owner Shahid Khan said.
"I thank Rene for accepting and now we move forward. I have great confidence in Rene and high expectations for our squad to respond."
Meulensteen added: "I appreciate the faith Mr. Khan has put in me and will do my very best to honour his trust. We aim to get Fulham back on track, starting Wednesday night."
Jol succeeded Mark Hughes in 2011 and guided Fulham to ninth and 12th place finishes in his first two seasons.
However, Khan's takeover in July 2013 changed the landscape at Craven Cottage and following nine league defeats this season the former Tottenham boss has been deemed surplus to requirements.
"Today I spoke with Martin to thank him for his efforts on behalf of Fulham Football Club over the past three seasons and, in particular, since my becoming Chairman earlier this year," Khan added.
"Martin was very gracious and I appreciate his understanding of the situation. There is no question Martin is an excellent football man and he has my utmost respect for the commitment he made to our Club.
"However, our poor form and results this season are undeniable, and Fulham supporters deserve better. With more than half the season still ahead, an immediate change was necessary."