Cano only played three innings on a night most of the Mariners starters departed early, with split-squad day games on the schedule for Saturday.
The Padres stuck with their first-teamers longer, and Venable, Yonder Alonso, Ryan Jackson and Kyle Blanks each had a pair of hits, while Jackson totaled three RBIs.
Kennedy went 5 2/3 innings in his longest start of the spring, holding the Mariners to three hits and two runs with two walks and seven strikeouts in a 95-pitch night.
Cano doubled home Brad Miller in the bottom of the first off Kennedy after Miller laced a one-out single. Miller, competing with Nick Franklin for Seattle's starting shortstop job, went 2-for-3 with an RBI double of his own in the fifth and is hitting .463 (19-for-41) with 10 extra-base hits.
Mariners lefty James Paxton gave up four hits and three runs in a four-inning start, with two walks and four strikeouts. Paxton threw 70 pitches in his second-to-last start of the spring and his Cactus League ERA rose to 3.18. His final start will come in a Minor League game Thursday to keep him on schedule, since the Mariners are off that day.
"It wasn't my best outing," Paxton said. "I struggled with my command a little bit. I was working on some off-speed stuff and getting behind in the count and left a few balls up. But my arm felt good and I felt like I made some good pitches. I'm ready for my next time out."
Padres third baseman Chase Headley, playing his second straight game since returning from a strained right calf muscle, went 1-for-4 with a line single off backup shortstop Chris Taylor's glove in the sixth and is now 1-for-6 for the spring.
Jackson ripped a two-run single with the bases loaded in the top of the second and Venable followed with a run-scoring double as San Diego jumped to a 3-1 lead against Paxton, who had allowed just three runs in 13 innings in his first four starts.
The televised game had instant replay in effect and the Padres challenged a pickoff throw over to first in the top of the fourth when Kennedy tried to catch pinch runner Leury Bonilla off the bag. But the ruling was upheld, with the umpires taking only about a minute to make their decision.
Mariners manager Lloyd McClendon also lost a challenge in the bottom of the eighth when an equally quick review was upheld after Blanks stretched to pull in a high toss to first from third baseman Alberto Gonzalez on a ground ball by Minor League outfielder Austin Wilson.
"We didn't have anything to lose," McClendon said. "It was 7-2 with two outs and that was the third out. We thought he probably stayed on the bag, but what the heck."
Up next: The Mariners have their final split-squad day of the spring with a pair of afternoon road games Saturday. Veteran right-hander Scott Baker gets the start against the A's in Phoenix in a 1:05 p.m. game that will be broadcast live on 710 ESPN Seattle and Gameday Audio. Young left-hander Roenis Elias makes his second start of the spring against the Rockies in a 1:10 p.m. contest at Salt River Field in Scottsdale, Ariz, in a game on MLB.TV. Both pitchers are non-roster invitees competing for one of the final rotation berths. Additionally, Taijuan Walker and Stephen Pryor will both make their spring debuts in Minor League games against the Padres at 1 p.m. at the Peoria Sports Complex as they return from injuries.