The US, who lost to Honduras in their opening game, face Costa Rica in Denver on Friday and Mexico at the Azteca Stadium on March 26 as they battle for a place in next year's World Cup finals in Brazil.
"We had to deal with injuries over the past few days and weeks," Klinsmann said. "But we have a roster that gives us the confidence to approach both games very positively. We have a group players coming in who have everything to get the job done."
Among the eight players missing through injury are first-choice goalkeeper Tim Howard (back), full-backs Steve Cherundolo (knee) and Fabian Johnson (hip) and midfielder Danny Williams (illness).
Klinsmann is also without Landon Donovan, the country's all-time top scorer, who is taking a break from the game and has not selected defender Carlos Bocanegra who is not featuring for his Spanish second division club Racing Santander.
The US coach defended his decision to leave out the experienced 33-year-old Bocanegra, who has 110 caps but did not feature in the 2-1 loss to Honduras last month.
"The reason he is not here is simply that he is not playing, not getting any minutes with Racing, he has no flow, no rhythm," said Klinsmann.
"He understands the situation. Carlos is still in the picture, this is not the end of his national team career but he understands that he is right now behind other players.
"It has been a very positive approach from Carlos, very professional and shows his great character - we will play it by ear over the next few months."
Klinsmann called the Costa Rica game a "must win" for his side ahead of the tough task that awaits in Mexico City where the US have never won a qualifier.
Several among those called up as replacements come from North America's Major League Soccer with Real Salt Lake's Tony Beltran and San Jose Earthquakes' Justin Morrow both named as full-back options despite making just one friendly appearance for the Stars and Stripes.
Aston Villa goalkeeper Brad Guzan is expected to start in place of Everton keeper Howard.
Klinsmann has plenty of options in attack and in midfield but he will have to field a new-look defence with midfielder Maurice Edu an option to drop back into a central defensive role to add some experience.
Beltran and Morrow, who featured in the goalless friendly draw with Canada in a January game for back-up players, are the only out-and-out full-backs in the squad and Klinsmann expressed confidence that they could cope with a high-pressure qualifier if called on.
"Those are two guys that play that position day in day out in their clubs," said Klinsmann.
"I looked at them in the January camp, I think they have the quality to come up to another level now but we also have other options coming out of midfield."
Goalkeepers: Brad Guzan (Aston Villa), Sean Johnson (Chicago Fire), Nick Rimando (Real Salt Lake)
Defenders: Tony Beltran (Real Salt Lake), Matt Besler (Sporting Kansas City), Geoff Cameron (Stoke City), Omar Gonzalez (LA Galaxy), Clarence Goodson (Brondby), Justin Morrow (San Jose Earthquakes)
Midfielders: DaMarcus Beasley (Puebla), Kyle Beckerman (Real Salt Lake), Michael Bradley (AS Roma), Joe Corona (Tijuana), Maurice Edu (Bursaspor), Jermaine Jones (Schalke 04), Sacha Kljestan (Anderlecht), Brek Shea (Stoke City), Graham Zusi (Sporting Kansas City).
Forwards: Jozy Altidore (AZ Alkmaar), Terrence Boyd (Rapid Vienna), Clint Dempsey (Tottenham Hotspur), Herculez Gomez (Santos Laguna), Eddie Johnson (Seattle Sounders)
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