Samardzija, set to be the Cubs' opening day starter, struck out seven. He allowed four runs and nine hits.
Samardzija hit a solo homer and an RBI single. Alfonso Soriano and Brad Nelson also homered for Chicago, and David DeJesus had two hits and drove in a run.
Justin Smoak homered and had a sacrifice fly for the Mariners. Jason Bay and Raul Ibanez added RBI singles.
Jon Garland, bidding to win a spot in the Seattle rotation, went six innings and gave up two runs on five hits with a walk and three strikeouts.