Armstrong, who has won cycling's signature race seven times, posted a statement on his Twitter page saying, "This will be (my) final Tour de France. It's been a great ride. Looking forward to 3 great weeks."
The cycling legend is riding for Team RadioShack this year. The team gained a Pro Tour license last fall and began competing this year.
Armstrong, 38, left cycling in 2006 but returned last year, partly to further his cause of cancer awareness. He finished third while riding for the Astana team, which is based in Kazakhstan.
He last won the Tour de France in 2005, the final of his seven consecutive championships.
This year's race begins Saturday with a warm-up in the Netherlands.