The 48-year-old Welshman, replacing Neil Warnock who was sacked on Sunday (local time), has signed a two-and-a-half-year deal at the Loftus Road club who are hovering one place and one point above the relegation zone.
"It's a great feeling to be back in football and to be the manager of QPR," former Manchester United and Chelsea striker Hughes, nicknamed Sparky, said on the club website (www.qpr.co.uk).
"I'm fully aware of the challenge in the short and long term and I am genuinely excited about the ambition of the owners."
Media reports said he has been promised money to spend on new players by Malaysian owner Tony Fernandes, who welcomed his arrival at the west London club who won promotion to the top flight last season.
"Mark has a proven track record in the Premier League, bringing a wealth of experience at both club and international level," Fernandes said.
"His ambitions match those of the board and we are delighted to have him at the helm."
Hughes resigned as manager of Fulham in June after just 43 games in charge, having led the London side to eighth place in the Premier League and a Europa League spot via the Fair Play League.
After taking Wales to the brink of the Euro 2004 finals, Hughes's first Premier League coaching assignment came with Blackburn Rovers, the club at which he finished his playing career.
Hughes spent four years at Rovers before joining Manchester City in 2008 shortly before they were taken over by billionaire Sheikh Mansour bin Zayed Al Nahyan.
Tasked with taking City into the Champions League, Hughes was sacked in December 2009 despite them being well-placed in the Premier League. He was replaced by Roberto Mancini.
He joined Fulham in July 2010 following the departure of Roy Hodgson to Liverpool before quitting less than halfway through a two-year contract, citing a desire to "further his experiences".
Hughes's most pressing task will be to ensure Premier League survival for QPR, who have won only one of their last 12 league matches.
"Now the immediate priority is to consolidate our place ... but beyond that, the future is very bright and fills me with great enthusiasm," he said.
Hughes will take charge of first-team training later on Tuesday and his first match will be Sunday's Premier League trip to seventh-placed Newcastle United.
