Cruz, who signed a four-year, $57 million deal after leading the Majors with 40 home runs last year for Baltimore, went 2-for-3 and took San Diego right-hander Ian Kennedy deep in the third with a two-run shot to left.
Cano, preparing for his second season with Seattle, went 2-for-3 with a double and two runs scored whle hitting in the No. 3 spot in front of Cruz as the Mariners started a lineup that looked close to a potential Opening Day nine.
Patrick Kivlehan, who had the game-winning RBI in Wednesday's 10th-inning win for Seattle, launched a three-run homer to left-center in the eighth, and San Diego second baseman Taylor Lindsey slugged a solo home run to center in the top of the ninth off Joe Saunders for the Padres' fourth run.
Seattle's starters put up six hits and three runs in the first three innings off Andrew Cashner and Kennedy. Cashner, last year's Opening Day starter for San Diego, allowed three hits and a run in his one scheduled frame while throwing 24 pitches.
Kennedy got the next two innings of work and surrendered three hits and two runs while throwing 46 pitches.
Seattle southpaw Roenis Elias, fighting for a spot as the No. 5 starter after winning 10 games last year as a rookie, threw two scoreless innings while allowing three hits and a walk. Elias benefitted from a pair of double plays in a 24-pitch outing.
Up next for Mariners: Right-hander Erasmo Ramirez makes his Cactus League debut as Seattle travels to Glendale to face the Dodgers in a 12:05 p.m. PT game at Camelback Ranch. Ramirez, 24, needs a big spring to force his way into contention in the Mariners deep rotation competition, but he is coming off an outstanding Winter League performance in Venezuela and has gained Major League experience with 47 outings over the past three seasons. The game will be broadcast live on Gameday Audio and televised on a delayed basis by the MLB Network.
a href="mailto:email@example.com">Greg Johns is a reporter for MLB.com. Follow him on Twitter @GregJohnsMLB as well as his Mariners Musings blog. This story was not subject to the approval of Major League Baseball or its clubs.