SAN DIEGO (AP) -- The Houston Astros were one strike away from opening the season with three straight losses, then inches away.
"Our bats woke up," manager Cecil Cooper said. "We got some big, big, big hits."
None was bigger than Berkman's homer. It was his first career hit off Hoffman, baseball's career saves leader.
"I just wanted to not strike out on three pitches like I did last night," said Berkman, who fanned against Hoffman to end Tuesday night's game.
With the Padres leading 6-5, Hoffman retired the first two batters before walking pinch-hitter Jose Cruz Jr. on a full-count pitch. Michael Bourn singled to right and Hunter Pence followed with a single off the tip of first baseman Adrian Gonzalez's glove to score Cruz. Berkman drove a 3-1 pitch to center field for his first homer of the season.
Berkman said he was able to pick up Hoffman's release point much better than he had on Tuesday, then patiently worked the count.
"He gave me a fastball that I could hit 3-1 and I'm glad I swung at it," Berkman said.
"Lance just crushed that one," Cooper said. "That ball was almost on a line going out of the ballpark."
Fans saw a rare sight -- Hoffman (0-1) being pulled. He blew the save a night after getting his first save of the season and the 525th of his career.
"It's part of the process and here we are talking about being on the other end of it," Hoffman said. "We had done a good job of shutting them down for almost three games, but they exploded for four runs in the ninth."
The Astros had scored just one run in their first two games, and that was on a bases-loaded walk.
Padres manager Bud Black called Berkman "one of the best players in the National league. He's a good hitter and good hitters do those things."
Balls were flying out of spacious Petco Park on a cold night. The Astros hit four homers and the Padres had two.
The Astros had tied the game at 5 in the top of the eighth when Berkman hit a leadoff double, stole third and scored on Miguel Tejada's sac fly.
Greg Maddux made five nice defensive plays in his season debut for the Padres, including one where he dove to his right to field Berkman's sharp grounder, got up and threw him out to end the fifth inning. Maddux won his record 17th Gold Glove Award last year.
"Just luck," Maddux said. "That's about the only time a pitcher can dive on a ball like that. It looks tougher than it is."
"I felt good, but just couldn't keep it in the park," Maddux said. "I made a couple of mistakes and they got me. It's probably one of the better lineups we'll face this year."
Maddux went six innings, allowing four runs, three earned, and six hits while striking out three and walking none. He turns 42 on April 14.
After winning the first two games of the four-game series, the Padres quickly fell behind 3-0.
Blum and Wigginton started the second with consecutive homers. Blum, who left the Padres as a free agent, hit a pitch into the seats in right field. Wigginton, who grew up in a San Diego suburb, drove a 3-2 pitch off the balcony on the fourth level of the Western Metal Supply Co. brick warehouse in the left-field corner for a 3-0 lead.
Hairston homered leading off the second and Giles added an RBI single. Gonzalez's two-run homer into the sand play area beyond the fence in right-center that gave the Padres a 4-3 lead.
Houston tied it on Lee's homer to center leading off the sixth.
Tony Clark hit into a double play while pinch-hitting for Maddux in the sixth, but Giles singled in Barrett, who opened the inning with a base hit to left.
Rodriguez allowed four runs and eight hits in five innings, struck out six and walked one.
The Padres repainted the third base coaching box at Petco Park on Wednesday, extending it about 20 feet toward home plate. The move came on the same day Los Angeles Dodgers third base coach Larry Bowa -- a former Padres manager -- was suspended for three games and fined by the commissioner's office following a wild argument the night before. Bowa was tossed in the sixth inning against the San Francisco Giants by umpire Ed Montague, who had told him to keep within the boundaries of the coaching box.