The Mariners had won three in a row until Wednesday's 2-1 loss, as Everth Cabrera scored on pinch-hitter Tommy Medica's RBI single in the bottom of the eighth inning to lift the Padres.
Charlie Furbush was dealt the loss and Mariners starter Felix Hernandez pitched well in the no-decision, striking out 10 and allowing one run and three hits in seven innings.
"Those things happen. They had their best guy on the mound and we had our best guy on the mound," said Mariners manager Lloyd McClendon. "Every time we don't score runs for Felix, we can't say it's a tough game for Felix. It's a tough game for the Seattle Mariners. It was a baseball game. It was unfortunate we came out on the short end of the stick today."
Brad Miller had two hits and an RBI for Seattle, which lost for the sixth time in the last nine tries.
The Mariners will visit Kansas City for three games this weekend and are scheduled to send Erasmo Ramirez to the mound Thursday. Ramirez is just 1-4 with a 5.27 ERA and has recorded three straight no-decisions. In Saturday's 4-3 loss to Texas, He tossed five shutout innings, walked four and struck out four batters.
Ramirez has pitched 9 2/3 scoreless innings and lost his only career start against the Padres back on June 14, 2012.
San Diego had lost three in a row and eight of nine games until squeezing out a win Wednesday. Joaquin Benoit picked up the win in relief with a scoreless eighth inning and Huston Street closed the door in the ninth for his 19th save.
Padres starter Andrew Cashner held the Mariners to a run in seven innings.
"I think one of the biggest things I did tonight was keep my focus," said Cashner.
The Padres honored the late Tony Gwynn before Wednesday's game. The No. 19 of "Mr. Padre" was adorned all over Petco Park and a video montage of Gwynn's memorable moments was shown on the big screen prior to the game. The Hall-of- Famer passed away Monday at the age 54 following a bout with cancer.
San Diego is slated to host Los Angeles for three games this weekend, but hopes Jesse Hahn can find more success when he toes the rubber Thursday. Hahn lost his major league debut June 3 versus Pittsburgh, but rebounded in Saturday's 5-0 road win against the New York Mets.
Hahn gave up one hit over six scoreless innings, striking out seven and walking three batters.
San Diego split four games with the Mariners last season.