But Furbush replaced Iwakuma in the eighth and gave up back-to-back doubles to Jose Altuve and Jason Castro leading off the frame. Houston pushed across another run when Brandon Barnes dropped down a squeeze bunt that turned into a single when Seattle had no one covering first.
"It's one of those things right when I saw the runner take off, I took off immediately, hoping he'd push the ball toward me," said rookie second baseman Nick Franklin. "I ended up being wrong in that case and I was supposed to cover first. It's just a mistake you learn from. It's the first time that's ever happened to me. It's something to learn from, which is key."
"Those are the things these young men are going through up the middle," Mariners skipper Eric Wedge said of his two rookie infielders, Franklin and Brad Miller. "Things that happen once that shouldn't happen again."
By that time, the Mariners were already down a run, however, after the consecutive doubles. Furbush said he made a good pitch to Altuve, but the diminutive second baseman drove it down the right-field line.
"Can't do much about that," said Furbush. "It was the pitch I wanted to throw. He went and got it."
Castro's RBI double was a different matter.
"I just left it down the middle," said Furbush, who leads the team in holds with 16, but fell to 2-5 with a 3.31 ERA with the loss.
The Mariners' bullpen had thrown 11 scoreless innings in the series to that point, so pitching hardly has been the problem. Lack of offensive support again loomed large as Seattle's struggles against left-handers continued.
Though they beat southpaw Dallas Keuchel, 3-1, on Saturday, Seattle has gone 19 innings without an extra-base hit since Dustin Ackley tripled in the eighth inning of Friday's victory.
"Their guy was really good today," said Wedge. "Iwakuma was strong, too. He had something on the end of his pitches and really did a good job. And their guy did a great job against us. He was a strike thrower, he had good stuff, used all of his pitches. I felt like he could throw anything at any time. Equally effective against right-handers and left-handers. I was impressed."
Oberholtzer, making just his sixth Major League start, threw the Astros' first complete game of the season with his four-hit shutout. The 24-year-old is 4-1 with a 2.79 ERA.
The win snapped a five-game losing streak for the Astros, while Seattle fell to 62-74. The Mariners still haven't swept a four-game series since July of 2012 when they took four from the Royals in Seattle.
Despite the loss, Seattle's starters dominated the Astros, going 3-0 with a 0.78 ERA (two runs in 23 innings) in the four games even without Felix Hernandez taking a turn. Hernandez kicks off a four-game set Monday afternoon in Kansas City.
Iwakuma allowed six hits and no runs over his seven innings with one walk and seven strikeouts. His record remains 12-6, while his ERA lowered to 2.92. The 32-year-old from Japan is 2-1 with a 1.38 ERA in four starts this year against the Astros with seven walks and 33 strikeouts.
"He's given us trouble all year," said Castro, the Astros' catcher. "He's got a great mix of pitches. He keeps you off balance, messes with your timing. His split is tough."
Iwakuma worked his way out of trouble several times, getting groundouts from right fielder L.J. Hoes to end the second and fourth innings with two runners on. Franklin helped out with an excellent diving stop to his right to deny Hoes on a sharp grounder up the middle with runners on second and third in the fourth frame.
"That is a very aggressive team and we know they'll swing first pitch," Iwakuma said through translator Antony Suzuki. "So I was keeping the ball down and relying on the movement on my sinker and my split-finger late in the count."
But the Mariners made little headway against Oberholtzer, as he gave up just four singles and allowed only one runner past first base. The youngster finished with one walk and five strikeouts while throwing 113 pitches.
Seattle's hitters came in with limited knowledge of Oberholtzer, but left with some new-found respect.
"I faced him one time in Triple-A, that's about it," Franklin said. "The first time he threw a lot of changeups, but he mixed in his curveball today. That was something new.
"With his fastball at 90 mph, it's not the typical 90. It's a little sneaky. But I don't think he was nibbling. More than anything, he was coming right after us with the fastball and attacking us late with the off-speed and trying to get us to chase upstairs."
The Mariners are now 10-6 against their new American League West rivals, with one three-game series remaining on the next homestand in Seattle.