Murphy's three-run homer, a towering 404-foot shot into the second deck in right field, put Texas up 6-1 against Walter Silva (0-1), who gave up nine runs in 2 1-3 innings. It was Murphy's third homer in eight games.
Before winning 9-8 in 12 innings at Arizona on Thursday night, when Murphy's solo homer was the difference, the AL West-leading Rangers had scored two runs or less in four consecutive games. They had gone 21 straight games without scoring more than six runs, their longest such streak since 1990.
Blalock homered leading off the fourth for a 10-1 lead.
Rangers rookie shortstop Elvis Andrus had four hits, including a bunt single and an RBI triple.
Millwood (8-5) allowed two runs over six innings, throwing 113 pitches in a game that started when it was 100 degrees.
The only loss at home by the right-hander was April 18, a 2-0 complete game against Kansas City and Zack Greinke. Millwood is 6-1 with a 2.17 ERA in nine home starts, allowing more than three runs only once.
Silva walked four and gave up seven hits. The 32-year-old right-hander made his fourth major league start for a depleted Padres staff that has six right-handed pitchers on the disabled list, including starters Chris Young and Jake Peavy.
The Padres, in a stretch of 20 games in 20 days before the All-Star break then with 25 games in 25 days after that, are 10-26 on the road. They are 3-10 in interleague games this season after losing their last eight games against AL teams last year.
Tony Gwynn Jr. led off the game with his first career homer, coming in his 161st game - 31st with the Padres.
But an error by Gwynn in the bottom of the first helped Texas go ahead to stay.
After Ian Kinsler had a leadoff double, Murphy hit a ball to right that ricocheted off Gwynn's glove for a two-base error that sent Kinsler home. Murphy scored on Blalock's sacrifice fly for a 2-1 lead.
Gwynn made a spectacular play against Murphy in the seventh with a sliding catch in foul territory. After scrambling to his feet, Gwynn doubled off Andrus at second base.
Adrian Gonzalez, traded from Texas to San Diego with Young three years ago, walked in his first two at-bats to increase his majors-high total to 61. Gonzalez has walked 30 times in June, four off the Padres' record for the most in a month.
Gonzalez was robbed of a hit when center fielder Marlon Byrd went fully extended parallel to the ground to make a diving catch in the gap to end the seventh.
NOTES: Gwynn's first career homer came 12 years to the day after his father, Tony Gwynn, hit an inside-the-park grand slam for the Padres. ... Padres manager Bud Black said Young (strained right shoulder) is on schedule to return to the rotation after the All-Star break and Peavy (strained right ankle tendon) will be medically evaluated Tuesday. ... RF Will Venable was a late scratch for San Diego because of a sore left wrist sustained in batting practice. ... Rangers CF Josh Hamilton, recovering from abdominal surgery, ran the bases before the game.
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