Brett Myers posted back-to-back wins for the run homer, as the Astros 1, in Roy Oswalt's return to Houston.
Oswalt (7-9), the second-winningest pitcher in Astros history, was touched for 11 hits and five runs in an unsuccessful return to his stomping grounds.
Myers (5-13) countered with eight innings of one-run ball, allowing just six hits in the opener of a three-game series.
"We can beat the better teams on any given night," Myers said. "Hopefully we keep it up."
The NL East-leading Phillies had a shot to clinch a playoff spot as a result of the Cardinals losing on Monday, and they held the early lead on Pete Orr's RBI single in the second inning,
But Oswalt simply didn't display the arsenal he showed off frequently during his 10-year stint in Houston. The veteran right-hander never retired the side over his seven frames, and yielded run-scoring hits to Humberto Quintero and Jimmy Paredes in the fourth.
Lee took an 0-2 hanging breaking ball over the wall in left for a two-run shot in the sixth, and Brian Bogusevic tacked on an RBI groundout an inning later.
Myers, also pitching against the team he broke into the majors with, threw 71 of his 107 pitches for strikes, as the Astros won for just the third time in 10 games.
"He's played with us and he knows how to pitch to us. He did a tremendous job," Phillies manager Charlie Manuel said of Myers.
Philadelphia has dropped consecutive games on the heels of a six-game winning streak.
Hunter Pence, traded from Houston to Philadelphia at the trade deadline, received a standing ovation from the Minute Maid Park crowd and went 2 for-4...The Phillies' Joe Blanton tossed a scoreless eighth in his sixth career appearance out of the bullpen...Jimmy Rollins was in the Phillies' starting lineup for the first time since August 21. A groin strain sidelined the shortstop for several weeks...Quintero and J.D. Martinez each had three hits for Houston...Game time: 2:22.