Lee drove an 0-1 pitch into the left-field porch for the Astros' second win in their last at-bat in three days. On Tuesday, Lance Berkman hit a two-run single in the ninth to lift the Astros to an 8-7 win.
The Astros have come from behind to win in 13 of their 20 victories this season.
"That's important going forward," Berkman said. "We've got to believe that no matter what the circumstances are, we have a chance to win it."
Michael Bourn started Thursday's comeback with a double to center. After Jeff Keppinger grounded out, Berkman drove a sinking liner that dropped at Guzman's feet and bounced away. Washington manager Jim Riggleman moved Guzman from shortstop to the outfield on a defensive switch an inning earlier.
Guzman said he lost the ball in the lights.
"It's a tough play for a normal outfielder. More for me," Guzman said. "If it's coming from a little bit outside [the lights], we can do something. The ball coming from right in the middle of the light, it's not easy."
Riggleman said he moved Guzman to right field because he had more speed than the alternative, Mike Morse, who pinch hit and scored a run in the top of the ninth. Guzman has seen time at shortstop, second base and right field this season.
"He's done a great job for us wherever we've put him," Riggleman said. "It turned out to be a miserable day for us."
Before the error -- his third of the game -- Guzman was on track to have the winning hit. His single gave the Nationals a 4-3 lead in the top of the ninth off Astros closer Matt Lindstrom.
Lindstrom (2-1) got the first two outs of the inning before Morse singled. Willie Harris then dropped a blooper just inside the left-field line, and the ball bounced over Lee and rolled toward the corner.
"It was a tough break there," Lee said. "They hit a ball that barely hit the line and took a funny hop. I was trying to stop them from getting extra bases to keep the guy from scoring. It bounced over my head."
Guzman committed two errors playing shortstop before the pivotal mistake in the outfield.
"Making an error, losing a game like that, it's really hard," Guzman said.
The Astros salvaged a solid effort by starter Brian Moehler, who allowed two runs on five hits in 5 1/3 innings. Moehler made his second start in place of Bud Norris, who's on the disabled list with bursitis and right biceps tendinitis.
Washington starter J.D. Martin allowed two earned runs and eight hits with four strikeouts. He may be the odd man out when the Nationals bring up 21-year-old phenom Stephen Strasburg to start Tuesday's game against Pittsburgh. Strasburg made his last minor-league start on Thursday, allowing no runs on three hits in five innings for Triple-A Syracuse.
Keppinger reached on Guzman's throwing error in the bottom of the first, the fourth error by a Washington shortstop in two games. Rookie Ian Desmond committed three in Wednesday's 5-1 loss.
Keppinger went to third on Berkman's single and scored on Lee's single. The Nationals have allowed 28 unearned runs in 32 games and their 50 errors lead the majors.
"The number of errors is misleading, but we haven't played good defense in the last week," Riggleman said. "I don't have an explanation for it. I know we work hard at it. I don't know if we're not concentrating enough pitch-to-pitch, I don't know what's going on."
Kevin Cash homered into the left-field porch in the second, his first home run since 2008, when he played for Boston. Berkman drove another homer into the left-field seats in the third, his sixth of the season.
The Nationals cut the deficit to 3-2, but grounded into inning-ending double plays in the seventh and eighth, against Jeff Fulchino and set-up man Brandon Lyon. Lyon has not allowed a run in 21 of 25 appearances this season.
The Astros are 13-1 when leading after seven innings. ... Riggleman said left-hander Scott Olsen will probably make a rehab start next week. ... Nationals 1B Adam Dunn said he wasn't surprised that Ken Griffey Jr. retired on Wednesday. Dunn and Griffey played together in Cincinnati from 2001-07. "He was the greatest player in the game, and I was just a little peon," Dunn said. "But it didn't matter who you were. He was always happy to help you. He just fit in with everyone. He wasn't your typical superstar. He was an awesome teammate."