Harden struck out nine over six innings and Brown hit a three-run homer to lead Oakland over the Boston Red Sox 5-1 Wednesday night.
"Last night we lost a heartbreaker. We won tonight. Now everyone's looking forward to getting back to the Bay Area and recovering," Oakland manager Bob Geren said.
Boston began its World Series title defense by winning Tuesday's opener 6-5 in 10 innings after rallying in the ninth. The Red Sox headed to Los Angeles after the game for three final spring training games against the Dodgers, including one at the Los Angeles Coliseum on Saturday.
"We'll take a step back tomorrow and have an optional workout," Red Sox manager Terry Francona said. "We tried to do our homework on what to expect from travel. We're not going to talk ourselves into being tired, and will do what we need to do to get ready for the next start in Oakland."
The Red Sox and A's resume their regular seasons with a two-game series starting Tuesday in Oakland. The Chicago Cubs and New York Mets split their Japanese series in 2000, as did the New York Yankees and Tampa Bay Rays in 2004.
Since the teams arrived last week, the focus was on the Red Sox, coming off their second title in four seasons, and Oakland was almost an afterthought. Indeed, late in the game, an Oakland flag above the scoreboard in center fell and landed on the warning track while the teams were changing between innings. A groundskeeper went out and retrieved it.
Harden (1-0) helped the A's gain something from the trip. Coming back from three injury-filled seasons, he made just four starts last year -- none after July 7. He allowed three hits and three walks, throwing 95 pitches.
"I had some bad luck the past couple of years," Harden said. "But, hopefully, I can put that behind me and do what I need to do to help the ballclub this season."
Harden said he tried to stay focused for Wednesday's game and not let the unique surroundings at Tokyo Dome affect him.
"You want to be consistent with how you approach your starts," said Harden. "It did feel a bit different out there, almost like a playoff game but you just try to treat it like any other game."
Oakland built a 4-0 lead against Jon Lester (0-1) while Harden for the most part dominated the Red Sox. Harden allowed his only run in the sixth on a homer by Manny Ramirez, who had struck out in his first two at-bats.
David Ortiz was 0-for-2 with a strikeout and a walk against Harden. Coming in, Ortiz was 4-for-5 against Harden and Ramirez was 2-for-3, each homering twice.
"Rich showed tonight against the world champions how good he is and how much we need him," Geren said. "His entire spring training went well with no health issues. We're hoping to get 30-plus more starts like that."
In the opener, Brown hit an RBI double in the 10th inning that pulled the A's within a run but was tagged between second and third. Two players followed his baserunning gaffe with hits.
"It's a great opportunity for me," said Brown, who made up for a costly baserunning mistake in Tuesday's loss. "We didn't play too bad last night, I made a mistake and it cost us. I was glad I could help the team today, so that we can head home with a win."
Ramirez struck out three times after hitting a pair of two-run doubles Tuesday. He stood at the plate admiring his 10th-inning drive in the opener, thinking it was a three-run homer, and had to hustle to reach second.
He could afford to stand and watch this one, a sure home-run deep into the left-field seats that moved him within nine of joining the 500-home run club.
Santiago Casilla, Keith Foulke and Alan Embree followed Harden with a scoreless inning apiece, completing a five-hitter for Oakland, which rebounded from its fourth straight opening-day loss. Foulke threw a called third strike past Ramirez to end the eighth with a runner on second.
Lester gave up four runs, five hits and three walks in four innings.
"Emil got one pitch just a little bit over the plate and he hit it over the wall," Lester said.
The crowd was much more subdued than it was during the opener, when Daisuke Matsuzaka pitched in his homeland for the first time since signing a $52 million, six-year contract with Boston before last season. ... Boston OF Brandon Moss was optioned to Triple-A Pawtucket after the game. He went 2-for-8 with two RBIs in the series.