Seattle trailed by three going into the bottom of the seventh, but Dioner Navarro hit a solo homer in that inning and the Mariners tied it in the eighth on an RBI double from Kendrys Morales and a run-scoring triple by Raul Ibanez.
The Mariners came up with the winning run in the 10th after Blake Parker (0-1) walked both Michael Saunders and Ibanez to open the inning.
The loss was the first major league decision for Parker, who was making his 17 relief appearance scattered over two seasons with the Cubs.
Yoervis Medina (3-2) needed only nine pitches to get through the top of the 10th and picked up the victory.
The Cubs slipped to 2-2 on a nine-game road trip.