The seven-times champion, whose hopes of an eighth Tour win were dashed after a crash in the Alps during stage eight, proved he was still a force to be reckoned with when he attacked from the gun in Bagneres de Luchon and stayed at the front all day.
While Armstrong finished sixth in the stage, six minutes and 45 seconds ahead of the peloton, Fedrigo gave France a sixth stage win in this Tour ahead of compatriot Casar.
Tour leader and holder Alberto Contador of Spain retained his eight-seconds overall lead from Luxembourg's Andy Schleck as the two favourites preserved energy for a potentially decisive showdown at the top of the Tourmalet in Thursday's 17th stage.
The long ride celebrated the 100th anniversary of the first stage in the Pyrenees and included the four climbs on the course that year, Peyresourde, Aspin, Tourmalet and Aubisque.
Fittingly Armstrong, the most celebrated rider on the Tour who came back after battling near-fatal cancer to win a record seven titles from 1999 to 2005, took centre stage while rivals Contador and Schleck played second fiddle at the back.
"It was hard from the start," said Contador. "On the first climb there were only a handful of guys left in the peloton. Afterwards, we worked to maintain the overall positions and we were able to do that."
Armstrong decided to leave his mark on his last Tour.
"I planned to attack. I knew straightaway on Peyresourde that it would be difficult and that a group was going to go away," he said. "It was full gas all day."
On the four climbs of the day, the Texan brought back memories of his glory days as he raced flat out with his black and red jersey wide open to his chest.
He was instrumental in the first break of the day, which involved almost all the disappointments of this edition -- Briton Bradley Wiggins, Czech Roman Kreuziger, Canada's Ryder Hesjedal and Spain's Carlos Sastre.
"It was more than a group because you had these guys -- Kreuziger, Hesjedal -- who were not GC (general classification) contenders but close enough. I knew that the peloton would not sit and let them go," Armstrong said.
But while the main pack, led by Contador's Astana team mates, worked to rein in so many great riders, they let Armstrong go when the decisive break took shape at the foot of the Tourmalet.
As befits a 100-year-old climb, the move was a veterans affair as it involved three of the four older riders in the bunch, Armstrong, Horner and France's Christophe Moreau, who was first to the top of the Tourmalet and Aubisque passes.
In the finale, only nine riders remained in the leading group, with a solid lead of almost nine minutes over the peloton.
"Lance had worked hard all day and he told me it would be difficult for the stage win," said his team manager Johan Bruyneel.
Spain's Carlos Barredo tried to part with his breakaway companions in the last 25km, only to be caught under the red flame marking the last km.
Armstrong raised himself up on his pedals and tried to go for the sprint but was forced to bow to his younger rivals.
Fedrigo was fastest, snatching the third Tour stage of his career.
"I thought I was about to miss my Tour as I was not feeling too well. Now this is a great moment, especially for the team," said Fedrigo, whose Bbox team mate Thomas Voeckler won the 15th stage.
(Editing by Pritha Sarkar; To query or comment on this story email firstname.lastname@example.org)