Raul Ibanez had two hits and two RBIs, and Ryan Howard and Jayson Werth drove in runs with key extra-base hits off 15-game winner Ubaldo Jimenez.
Lee, the reigning AL Cy Young Award winner, struck out five and had no walks in his first career playoff start. He retired 16 straight batters at one point until Garrett Atkins hit a wind-blown double in the seventh. Lee lost his shutout when Troy Tulowitzki singled in a run with two outs in the ninth.
Game 2 of the best-of-five NL division series is set for Thursday with Cole Hamels, last year's World Series and NLCS MVP, on the mound for the Phillies against Colorado's Aaron Cook.
Some questioned manager Charlie Manuel's decision to give Lee the ball over the playoff-tested Hamels for the first game. But Lee made his manager look brilliant with a masterful performance.
On a day when swirling winds made flyballs an adventure, Lee ignored the elements and shut down the NL's second-highest scoring offense. Avoiding the adventures that come with the Phillies bullpen, Lee mixed a deceptive fastball with off-speed pitches, had pinpoint accuracy and threw 113 pitches.
The hard-throwing Jimenez was equally impressive against the league's No. 1-scoring offense for four innings, but ran out of gas in the fifth. He got chased with no outs in the sixth after allowing nine hits and five runs in five-plus innings.
A sellout crowd of 46,452 - the largest in the six-year history of Citizens Bank Park - rocked the ballpark, waving their white-and-red "Fightin' Phils" rally towels. The Phillies were 7-0 at home last October and set a franchise attendance record this season.
Werth, one of five All-Stars in Philadelphia's lineup, got it started with a walk in the fifth. He scored when Ibanez ripped a double into the right-field corner. Ibanez's hit fired up the raucous crowd, which screamed "Rauuuuuuuul!" Carlos Ruiz followed with a single to right to make it 2-0.
The Phillies got insurance runs in the sixth. Chase Utley led off with a single and stole second. Howard lined a run-scoring double to left that mixed up Carlos Gonzalez, who fell backward into the wall.
Werth followed with a drive that hit high off the left-center field wall. Werth may have had a chance for an inside-the-park homer, but he trotted slowly to first before turning it on and settling for a triple after the wind kept the ball in the park.
Joe Beimel came in to face Ibanez, who singled in another run to make it 5-0.
That was plenty of support for Lee, who made sure everyone has to wait another day to see if Brad Lidge gets the chance to be Philadelphia's closer.
Just two years ago, Lee watched from the bench as the Cleveland Indians reached the ALCS. He was left off the postseason roster after a poor season in which he was demoted to the minors and relegated to the bullpen.
But he went 22-3 last year and was shipped to Philadelphia on July 29 when the cost-cutting Indians purged their roster.
Jimenez showed off his blazing fastball early. He reached 100 mph against the second batter, Shane Victorino. The 25-year-old right-hander didn't wait long to mix speeds, either. He froze Howard with an 80 mph curve ball for a called third strike in the second. He got Utley on the exact pitch in the fourth.
The Phillies have been on cruise control for a while, waiting to start the postseason and have a chance to be the first repeat champions since the New York Yankees won three World Series in a row from 1998-2000. Though they didn't clinch their third straight NL East title until the final week, it was never in doubt. Philadelphia moved into first place for good on May 30, and had a comfortable lead the rest of the way.
Colorado rebounded from an awful start and finished a franchise-best 92-70, including 74-42 after Jim Tracy replaced Clint Hurdle as manager on May 29.
NOTES: The Rockies are making their third postseason appearance in the franchise's 17 years. They swept Arizona in the 2007 NLCS before getting swept by Boston in the World Series. ... Kevin Bacon and his brother, Michael, sang the national anthem, wearing Phillies jerseys. ... Lee singled and stole second base with two outs in the third. It was the first ever steal by a Phillies pitcher in the postseason.