Shortstop Alcides Escobar tripled and scored a pair of runs for the Royals, while right-hander Kris Medlen gave up eight hits and four runs (two earned) in 4 1/3 innings.
Cano hit three homers with seven RBIs on Sunday against the Cubs in Mesa, then stayed hot with another blast -- his seventh of the spring -- in the fifth inning off Medlen, after Cruz cracked his fourth Cactus League homer leading off the fourth.
Karns, who learned he'd won the Mariners' final rotation spot when James Paxton was optioned to Triple-A Tacoma earlier in the day, wasn't helped by his defense, as two errors lead to a pair of unearned runs.