Cano has at least one hit in seven of his past eight spring training games, having missed four games after an emergency dental procedure last week. The Mariners second baseman is 12-for-19 this spring.
Cubs prospect Javier Baez homered and roster hopeful Mike Olt hit two home runs and drove in three runs.
Olt, a 2010 first-round draft pick, took Mariners starter Randy Wolf deep in the second inning for his first home run of the night. Baez tied the score at 2 with his home run off Wolf in the top of the fourth.
"He's got good bat speed and obviously he's got good power," Wolf said of Baez. "You leave the ball out over the plate and he's that strong, it's not going to be a cheap home run."
Olt started a four-run sixth inning with his second home run. Catcher John Baker finished 2-for-3 with a three-run double in the sixth.
Baker cleared the bases after three Mariners' errors in the inning.
Seattle shortstop Brad Miller helped his cause as he battles another young player, Nick Franklin, for the starting job. Miller homered, singled and drove in two.
Cubs starter James McDonald struggled with his control and got through just 2 2-3 innings, walking five.
"It's not always going to be 1-2-3," McDonald said. "One thing I can control is my effort and the way I compete."
Mariners catcher John Buck drove in the tying runs with a two-out single in the bottom of the ninth.
Abraham Almonte scored the winning run on a Ty Kelly single in the 10th.
"We executed at the end, we didn't do much executing in between. That's what spring training's all about," Mariners manager Lloyd McClendon said.
Chicago: McDonald didn't help himself much in his bid to be in the starting rotation. The positive he took from a five-walk outing was that he kept his team in the game and kept Cano in the ballpark, he said.
Seattle: Wolf allowed two runs and six hits with three strikeouts over four innings as he continues a bid to make the rotation. "Threw a lot of strikes. Got ahead of a lot of guys. I started throwing my slider and was able to get some outs with it," Wolf said. "For me, to get stronger every time out, throw strikes better than I did the time before, that's really what my goal is."
Chicago: Left-handed pitcher James Russell made his spring training debut after experiencing arm fatigue and gave up Miller's home run in his lone inning of work. He struck out one. Shortstop Starlin Castro is out with a hamstring injury but could be back sometime next week.
Seattle: Corey Hart was held out with forearm stiffness, but could return to game action this week.
Chicago: Olt is somewhat of a longshot to make the major league roster, but he's trying not to get ahead of himself after his 3-for-4 game. Baez is also bound for the minors at some point, though he survived a 10-player roster move Wednesday. His solo shot was one of the deepest hit at the Peoria Sports Complex this spring.
Seattle: Stefen Romero, the club's 2012 minor league player of the year, was a late-inning replacement Thursday and singled twice and scored. He has nine hits in his past 16 at-bats after starting the spring 0-for-16.
UPON FURTHER REVIEW
Wednesday's night's game was played with Major League Baseball's replay rules in effect, and Cubs manager Rick Renteria challenged a call at first base in the fourth inning. Chicago's Ryan Kalish was called out on a close play at first base following a ground ball to shortstop. The call was upheld and the review took about two minutes. It was the first challenge of spring training in three replay-eligible games.
MARINERS NAME TRIPLE-A MANAGER
Former major leaguer Roy Howell was hired as the new manager of the Mariners' Triple-A affiliate in Tacoma. Howell replaces Rich Donnelly, who was recently hired as third base coach. Howell began this year as the hitting coach for Double-A Jackson.
Chicago: The Cubs have Thursday off. Kyle Hendricks makes his fourth appearance of spring training on Friday against the Los Angeles Dodgers in Mesa, Ariz.
Seattle: Right-hander Blake Beavan is scheduled for his third start and fourth overall appearance of the spring against the Arizona Diamondbacks in Scottsdale.