Adam Jones' two-out, two-run double in the sixth moved the Orioles ahead of the Mariners, 3-2.
Jones ended a streak of 40 straight innings for the Orioles without a lead. They hadn't held one since the first inning of a May 5 game against the Royals.
Rookie Michael Pineda retired the first two batters before Vladimir Guerrero and Luke Scott singled. Jones followed with a double to left, giving him 18 RBIs this season.
Jake Arrieta was in line to get the win, but his replacement, Michael Gonzalez, gave up a two-out RBI double to Chone Figgines in the seventh.
Gonzalez hadn't been scored upon in his last five outings, but Michael Saunders snapped an 0-for-26 streak with a two-out single and Ichiro Suzuki reached on an infield hit before Figgins came to the plate.
Arrieta allowed two runs and four hits in six innings, with three walks and six strikeouts. He threw 103 pitches, 54 for strikes.
Tonight's attendance: 11,485
Instant update: Koji Uehara replaced Gonzalez with the bases loaded, and Miguel Olivo drove in the go-ahead run with an infield hit. Third baseman Mark Reynolds couldn't come up with the ball cleanly after lunging for it.
Mariners 4, Orioles 3.
Well, the lead was nice while it lasted.