The 26-year-old Contador stayed safe in the main bunch as the last stage, over 164 km from Montereau Fault-Yonne, went to Briton Mark Cavendish.
“I am really happy. It was an especially difficult Tour for me but that’s why I am enjoying the victory all the more,” Contador said on the podium.
Over three weeks, Contador proved the strongest rider in the mountains and in the time trials, beating Luxembourg’s Andy Schleck by four minutes 11 seconds.
Seven-times champion Armstrong, back from 3-1/2 years in retirement, finished third overall 5:24 off the pace.
Schleck, who also took the white jersey for the best under-25 rider, said: “He (Contador) was the strongest rider. He is the boss of the peloton.”
The victory kept the Spanish flag flying high on the Champs-Elysees following triumphs for Oscar Pereiro in 2006, Contador in 2007 and Carlos Sastre last year.
Contador, who missed last year’s Tour after Astana were not invited because of their past doping record, took the overall leader’s yellow jersey with a strong attack in the first Alpine stage in Verbier, Switzerland.
But throughout the three-week race, he had to contend with criticism from team mate Armstrong, who twice said publicly the Spaniard had ignored team orders.
“This Tour was very difficult as you could see and although it sometimes seems easy on television it wasn’t because of other factors,” Contador told Spanish television. “I will enjoy this second Tour win as if it was a double victory.
“The only thing I can tell you is that I will be here next year with a team that has the most secure guarantees and that is the most focused on winning this race.
“There are several possibilities but what is clear is that we are totally incompatible and Armstrong will go one way and I will go the other,” Contador added.
Armstrong stayed in contention for almost two weeks but he discovered his limits in the Alps and in the final time trial in Annecy, which Contador won.
It was the ninth Tour title for Astana’s Belgian team manager Johan Bruyneel, who masterminded Armstrong’s seven victories on the three-week race.
Cavendish outsprinted Columbia team mate Mark Renshaw of Australia and American Tyler Farrar at the end of the final stage to clinch his sixth win in this year’s race.
“I wanted so bad to reach Paris, my team mates helped me to this,” said Cavendish.
“And winning on the Champs-Elysees… All my dreams come true.”
Norway’s Thor Hushovd clinched the green jersey for the points classification and Italy’s Franco Pellizotti won the polka dot jersey for the best climber.
Britain had an exciting year on the Tour, with Cavendish snatching six stages and Bradley Wiggins finishing fourth overall.