Swiss organizers said on Tuesday that Team RadioShack confirmed Armstrong will compete in the June 12-20 event.
"We are really proud of having Lance Armstrong in the starting lineup," said Rolf Huser, spokesman for organizers IMG. "Lance is a big star. It's really important to have him."
The Tour de Suisse is one of the recognized final warmups for the three-week Tour de France, which begins on July 3.
Armstrong, a seven-time Tour de France winner, put the Swiss event on his race schedule after crashing in the Tour of California last month. He is also competing in the five-day Tour de Luxembourg starting Wednesday.
The 38-year-old American last raced the Swiss tour in 2001, when he won the event before taking the third of his seven straight Tour de France victories.
The Swiss route offers a balanced mix of flat and mountain terrain, peaking at 7,595 feet altitude at Albulapass near the St. Moritz ski station during the 132.4-mile stage six.
The race starts with a 4.7-mile prologue time trial in Lugano near the Italian border in the southeast of Switzerland, and finishes with a 16.7-mile individual time trial at Liestal near the German border in the northwest.
Armstrong will likely be rivaled for attention by home favorite and defending champion Fabian Cancellara.
"It's going to be interesting to see the difference between Fabian and Lance," said Huser, who also is Cancellara's agent. "There is the new generation and one of the biggest riders that cycling has."
Cancellara has said he is focusing on the time trials rather than overall victory, because he already achieved his season's top objectives by winning the one-day Tour of Flanders and Paris-Roubaix spring classics.
"These are the things that spur me on for the Tour de Suisse this year," the 29-year-old Olympic and world time trial champion said.