Cruz, who finished with two hits, was the Mariners' highest-profile pickup in the offseason after being an All-Star with Baltimore last year. He curled a pitch from Ian Kennedy near the left-field foul pole in the bottom of the third to give Seattle a 4-1 lead.
"Felix asked me for a home run," Cruz said of Mariners ace Felix Hernandez. "I said I normally don't hit homers in the spring but I'll try today. It was pretty close. The call was fair."
It was close enough for Padres manager Bud Black to come out of the dugout for a chat with plate umpire Brian Knight.
"I had foul ball," Black said. "These games don't count."
Will Venable hit a two-run homer for the Padres, who lost to Seattle for the second straight day. Alexi Amarista had three hits and an RBI.
Robinson Cano and Kyle Seager both had two hits, with Cano scoring twice and Seager scoring and driving in a run. Both also helped the Mariners turn two double plays.
Cruz is between Cano and Seager in the Mariners' projected opening day lineup.
"It was exciting to see the whole lineup," Cruz said. "See what we can do together."
Padres: Andrew Cashner allowed a run on three hits with a strikeout in the one inning he worked. Kennedy, another member of the projected starting rotation, allowed two runs on three hits — including Cruz's homer — with two strikeouts in two innings.
"I thought both their stuff was good," Black said. "Ian had good velocity. 'Cash,' his fastball and changeup combo."
Mariners: Roenis Elias, who went 10-12 with a 3.85 ERA for Seattle last season, is in competition for a spot in the starting rotation this spring. He allowed no runs on three hits with a walk in two innings. "I feel strong," Elias said. "I worked on my changeup, pretty much, and my fastball and command."
Mariners: 1B Ji-Man Choi, who broke his right fibula in Seattle's spring training opener Wednesday, was scheduled for surgery Thursday and will be out four-to-six months, manager Lloyd McClendon said.
THAT WAS EASY
The Mariners made a pitching change in the middle of the top of the third inning, with Danny Farquhar taken out due to a high pitch count and Justin Germano brought in from the bullpen. The count at the time of the move was 2-2 on San Diego's Will Middlebrooks, but Germano needed only one pitch to record a strikeout and end the inning, stranding two runners.
WHERE THERE'S A WIL(L)
The Padres' starting lineup consisted of three players named either Will or Wil.
Center fielder Wil Myers made his Padres spring training debut — he was acquired in trade with Tampa Bay in the offseason — and went 1-for-3. Venable started in right field and Middlebrooks, picked up in a trade with the Boston Red Sox last December, was 1-for-3 in his first game with the Padres and played third base.
The Padres also have catcher Wil Nieves on their spring training roster.
Padres: RHP Odrisamer Despaigne (4-7, 3.36 ERA in 2014) is scheduled to start against the Chicago White Sox in Peoria on Friday. RHP Brandon Morrow, in competition for a starting rotation spot with Despaigne, is also expected to pitch.
Mariners: RHP Erasmo Ramirez is the scheduled starter Friday against the Los Angeles Dodgers in Glendale, Arizona, in his bid to make the starting rotation. Ramirez, 24, went 1-6 with a 5.26 ERA last season for Seattle.