Roenis Elias pitched into the seventh inning and Franklin Gutierrez hit a two-run homer in the Mariners' 4-2 loss to the White Sox on Thursday night.
Seattle went 0 for 6 with runners in scoring position and let seven on base.
"We had opportunities early. We didn't take advantage of them," Mariners manager Lloyd McClendon said. "We had opportunities throughout the game and didn't take advantage.
Elias (4-7) gave up four runs and nine hits in 6 2/3 innings. Making his first start since July 2, he remained winless since beating Houston on June 19.
"First two innings there was a couple of hiccups with his spots but other than that once he got in his groove he was great," catcher Mike Zunino said.
Chicago's Carlos Rodon (6-5) took a shutout into the seventh inning but left after giving up a two-run homer to Franklin Gutierrez. He was charged with both runs and three hits while striking out five and walking three in six-plus innings.
After Rodon left, Mark Trumbo singled and Seth Smith doubled but Zach Duke struck out Brad Miller and Zunino before getting Ketel Marte to fly out to center. Seattle also had a chance in the eighth after getting runners to second and third with two outs, but Trumbo grounded out to second.
David Robertson got the last three outs for his 27th save in 33 chances.
Nelson Cruz went 1 for 4 and extended his streak of getting on base to 37 games with a third-inning single. The streak is the American League's longest this year.
Seattle snapped a two-game win streak in the opener of a 10-game, 11-day road trip.
Adam Eaton had three hits and scored three runs while Jose Abreu and Trayce Thompson had RBI doubles for Chicago. The White Sox wore throwback uniforms that debuted in 1976 and included white wide-collared untucked jerseys paired with navy blue pants and white socks.
"(Eaton) probably wants to wear these all the time," Chicago manager Robin Ventura said.
Eaton reached base four times and his three runs were a season high.
Thompson had two hits and Avisail Garcia added two RBIs for the White Sox, who had lost three of their previous four.
McClendon said INF Kyle Seager was getting a day off and would be back in the Mariners' lineup Friday. Seager pinch-hit for Zunino and grounded out to end the game after entering the day batting just .196 in August.
"He deserves (a day off) every now and then," McClendon said.
Seager said he was fine physically.
Miller batted eighth and played third base for Seattle.
DH Jesus Montero fouled a pitch off his midsection in the fifth and was pinch-hit for in the seventh. Montero said despite wearing protective equipment "it still hurt" but was feeling fine after the game.
Mariners: LHP James Paxton (strained left middle finger) is expected to make his next rehab start Friday at Triple-A Tacoma.
White Sox: Eaton was hit in the back in the fifth but stayed in the game.
Seattle RHP Taijuan Walker (9-7, 4.72) faces Chicago LHP John Danks (6-11, 4.90) in the second game of this series. Walker is 2-0 with a 3.71 ERA since his one-hitter July 31 at Minnesota, while Danks is coming off an Aug. 23 loss to Seattle when he allowed seven runs and eight hits over five innings.