The tie, being played on clay in Fribourg, is the pick of the first-round match-ups.
Federer v Isner will be Friday's second rubber after Switzerland's Stanislas Wawrinka has kicked things off by taking on Mardy Fish.
For Saturday's doubles rubber, the Swiss have nominated Federer and Wawrinka, while the USA, who are without Bob Bryan following the recent birth of his daughter, are due to field his twin brother Mike Bryan and youngster Ryan Harrison.
The reverse singles will follow on Sunday.
"I am in a good state mentally and physically,'' Federer said.
"I have had a great run since last year's US Open. Here in Switzerland, it is nice we got home-court advantage, and we will try to make the best of it and see where it takes us.''
Isner feels getting his famous first serve firing will be key to his chances.
"In any match, making a lot of first serves is important, especially for me. I am going to have to hit a high percentage to give myself the best chance of winning," he said.
"On top of that I am going to have to hit my second serves big. I just can't roll them in there because he can do everything. He can hit any shot in the book.
"I don't want to be getting in 15-ball rallies with Roger from the baseline cause that probably won't bode well for me so I'm going to need to play aggressive, play first-strike tennis and see how it goes."
Isner feels his side are certainly underdogs overall but feels the US can still triumph and reach the last eight.
He added: "Any time you are playing against a team that has Roger as part of the squad, it is going to be tough and we are not playing at home. But we are definitely capable of coming out here, playing well and coming out with a win."
The Davis Cup is one prize 16-time Grand Slam champion Federer has yet to win.
A Federer-led Switzerland reached the semi-finals back in 2003 but lost out to Australia after Federer blew a two-set lead against Lleyton Hewitt in a crunch rubber.
Holders Spain are shorn of all four players who secured the trophy in December's final, including Rafael Nadal.
Former world number one Juan Carlos Ferrero will open their 2012 campaign by taking on Kazakhstan's Mikhail Kukushkin. Nicolas Almagro will follow against Andrey Golubev. Marcel Granollers and Marc Lopez will play doubles for the Spaniards on Saturday.
Despite the absentees, new captain Alex Corretja, who has taken over from Albert Costa, is confident about his side's chances.
"(The players' absence) is not something I'm thinking about at the moment because I have the duty to build a team with the four players that we think are best suited,'' Corretja told the official Davis Cup website.
"I have the luck of having four big players that are very keen to play and that's what matters the most.
"There are others that could be here but are not, but I also thank them for their availability.''
The 2010 champions Serbia are without world number one Novak Djokovic for their home clash with Sweden but should still have few problems in reaching the last eight.
Janko Tipsarevic and Viktor Troicki have been chosen as their singles players for Friday's rubbers when both will start hot favourites in Nis.
Russia hand a debut to Alex Bogomolov against Austria. He will take on Andreas Haider-Maurer in the second rubber after Igor Kunitsyn has played Jurgen Melzer.
In Ostrava, a Tomas Berdych-led Czech Republic side will fancy their chances against Italy.
Top-10 star Berdych will play the second rubber against Simone Bolelli after Radek Stepanek has opened up against Andreas Seppi.
Germany will be without the ill Philipp Kohlschreiber for their home tie against last year's runners-up Argentina.
He has ben replaced by Cedrik-Marcel Stebe in their team, although Stebe has not been named by skipper Patrik Kuhnen for any of the rubbers.
Philipp Petzschner will kick off the tie against Juan Monaco before Florian Mayer takes on David Nalbandian in Friday's action.
The other first-round ties see Japan host Croatia and Canada entertain France.