The loss dropped Seattle below .500 for the first time this season at 7-8 as Texas (9-7) took three of four in the series.
Cano hit a three-run shot off Rangers starter Tanner Scheppers to get Seattle back in the game after Texas had taken a 4-0 lead on Ramirez. Cano's first home run came in his 15th game for Seattle and his first at designated hitter as manager Lloyd McClendon gave him a day off from his second-base duties.
"It feels good, not so much because it's my first one, but at least I hit the ball in the air," Cano said. "The last four games I hit in the air twice. Most of my swings, I've been hitting ground balls. Hopefully I'll start getting better pitches to hit.
"I don't want to sound cocky, but I've just been hitting whatever they give me because they pitch me in and out, in and out," said Cano. "I'm not getting many pitches over the plate. You have to deal with whatever and just be ready and patient."
The $240 million free agent went 1-for-5 with three RBIs and is now hitting .271 with eight RBIs on the year.
McClendon said he didn't think Cano had been pressing to get his first homer in a Mariners uniform.
"You look at his track record and numbers, I think he figured out a long time ago that he could hit," McClendon said. "I don't think he was panicking after 14 ballgames."
Cano didn't hit his first home run until his 12th game in 2012 with the Yankees and went on to post a career-best 33 bombs that year, so indeed he wasn't counting off the days this April.
"I don't really worry about it," he said. "There's five more months in the season. Most of the good hitters hit a lot of their homers in two months out of the six. The first month they'll hit three or five and then in June and July they'll hit eight each month. Sometimes you want to rush to get where you want, but you have to be patient and play the game."
Hart immediately followed Cano with a solo blast of his own to left field in the third inning as his fourth home run of the year tied the score at 4. And things were looking up for the Mariners when Dustin Ackley made it 6-4 when he greeted reliever Hector Noesi with a two-run double after Scheppers was pulled three batters later.
But that six-run inning turned out to be the only scoring for the Mariners as they couldn't cross the plate against five Texas relievers.
Scheppers, the Rangers' Opening Day starter, went 2 1/3 innings with six runs, six hits and three walks as he fell to 0-2 with a 9.82 ERA in four starts.
But Ramirez wasn't any better for the Mariners as the right-hander lasted just two-plus innings with six hits, five runs and two walks before he got the hook from McClendon following a leadoff double in the third.
"Obviously I'm very disappointed," McClendon said. "I thought he'd shown signs of coming out of it, then he just reverted back to lack of command and quality pitches. When he did throw strikes, they were in the middle of the plate. It's very concerning and something we'll have to continue to work through and try to get him right."
Ramirez wound up with a no-decision and is 1-2 with a 7.50 ERA. The 23-year-old has allowed 18 hits and 13 runs over 11 innings in his last three outings after a strong opening debut against the Angels.
"I put stress on my team," Ramirez said. "I know I'm better than that. I can do it. I know it. I feel it. I just have to realize what I did and keep pounding the strike zone and find the right mechanic when I get ahead of hitters. If I need one pitch or two pitches, just go do it and don't be thinking too much about strikeouts. Just make them swing the bat and get ground balls or popups."
The Rangers knotted the game back up at 6 with a pair of runs in the third, knocking Ramirez from the game and tacking the tying run off rookie reliever Dominic Leone, who now has allowed one run in 8 1/3 innings in his first five appearances.
Veteran southpaw Joe Beimel took the loss after he replaced Leone and surrendered the lead with two runs in the fifth as Texas kept taking advantage of every opportunity, including a wild pitch with a runner on third for the second run.
McClendon said the bullpen has been taxed by some starting pitching hiccups and injuries are affecting the rotation with Hisashi Iwakuma, James Paxton, Taijuan Walker and Blake Beavan all on the disabled list, but he liked the way his club battled back after a walkoff loss Wednesday and then falling behind 4-0 in Thursday's finale.
"We've been dealt a tough hand, no question, but you deal with it," McClendon said. "We'll be OK. We're only 15 games into the season. I like the resiliency I saw today. We really battled back and never gave up, and that's a good sign. I think there are good things to come. I know this was a tough one and this series was tough for us, but it's not my first rodeo. I've been through it before. This club will be OK."