Vargas threw 50 pitches and did not allow a base runner.
The Padres, playing their spring training opener, committed three errors, two in the fifth inning that led to a pair of Mariners' runs.
Seager homered in the first inning off Padres starter Anthony Bass. Seager's two-out single drove in Chone Figgins in the third inning, and he reached on a hit and throwing error in the fifth that allowed Munenori Kawasaki to score from second base.
The Padres scored four runs in the top of the ninth off Mariners reliever Jarrett Grube to tie the score at 4. But Johermyn Chavez's double drove in Mike Wilson from first base for the winning run in the bottom of the inning.