The 47-year-old replaces Steven Pressley, who resigned on Tuesday.
Rosler's last job was as head coach of Leeds United, where he was sacked by chairman Massimo Cellino in October 2015 after just 12 games in charge.
The former East Germany international and Manchester City striker has also led Wigan, Brentford and three Norwegian sides.
"I had several options in the UK and abroad but I was waiting for an opportunity and challenge like this to come along," Rosler told the club website.
"The discussions I had with the owner Andy Pilley and technical director Gretar Steinsson really impressed me and I feel I can put my stamp on Fleetwood Town.
"The club is a huge success story so far and hopefully I can now help write a new chapter."
The Cod Army have had a swift rise up the English football pyramid - in 2005, they were celebrating winning the North West Counties Premier Division in the ninth tier.
Four promotions in seven seasons saw the club enter the Football League in 2012, and the Lancashire club moved into League One two seasons later when they won the play-off final at Wembley.
"He's a hugely experienced, respected and knowledgeable coach in the game and the fact we have been able to attract him to Fleetwood Town shows just how far we've come," said Pilley.
"We had an incredible level of applicants for the job and we are delighted to say Uwe was our number one choice.
"His attacking style of football is something which excites me and I'm sure excites the fans of Fleetwood Town. We are now looking forward to a new era at Highbury."
League One side Fleetwood Town have appointed Uwe Rosler as their new manager on a two-year deal.