The former Tottenham striker replaces Bob Bradley, who was sacked late last month after the team lost the Gold Cup final 4-2 to Mexico on home soil.
“This is a big moment for me personally and for my family,” Klinsmann said.
“I’m really proud to be given the opportunity to be part of the future of US soccer.
“It is going to be a challenge and it will be demanding. There is a game next week against Mexico.”
The 47-year-old former German international has lived in America for the last 13 years. His last job was with German giants Bayern Munich, whom he left in 2009.