The White Sox had just five hits on the day, but three cleared the fence and accounted for all four runs off starter Hisashi Iwakuma and Loe.
The Mariners, who pulled out their own 10-inning win in the first game of this series on Friday, wrapped up their initial road trip with a 3-4 record and return to Seattle for a 10-game homestand beginning with the Astros on Monday.
Morales went 3-for-4 with a double and home run, but the rest of the club was 4-for-33 with 10 strikeouts, including an 0-for-7 mark with runners in scoring position for a second straight game.
"I think we're definitely underachieving," said Morse, who accounted for four of the strikeouts after his first-inning homer. "We've only played, what, a week of baseball? But I think we've shown some signs of what we're capable of doing.
"We're not getting the base hits as much right now. No one has clicked yet, really. It's early and there's a lot of baseball left."
Viciedo, a 24-year-old Cuban who hit 25 home runs last year as a rookie, launched a 406-foot shot to left off Loe with one out in the 10th for his first career walk-off.
"I fell behind 2-0 and had to get back in the count and just left a sinker up," said Loe, a veteran right-hander in his first season with Seattle. "I meant for it to be away and it came back over the middle of the plate and he hit it well. You pipe it down the middle 2-0 to any of these big league hitters and they're probably going to put a good swing on it. It was a bad pitch."
The Mariners threatened in the top of the 10th with a two-out double by Michael Saunders. Reliever Addison Reed then intentionally walked Morales before striking out Morse.
"They're feeding off my aggressiveness right now," said Morse, who is hitting .310, but has 10 strikeouts in 29 at-bats. "I just need to relax a little bit and zone up a little more. Stay aggressive, but under control. I'm kind of swinging out of the zone a little bit. But like I said, it's way early and there's a lot of baseball left."
The loss spoiled a strong start by Iwakuma, who gave up just four hits in eight innings with no walks and three strikeouts. His outing was marred only by home runs to Adam Dunn in the first and Alex Rios in the seventh.
After Dunn's two-run bomb, Iwakuma retired 16 straight batters before Rios popped a solo shot to re-tie the game at 3.
"It's scary to pitch here," Iwakuma said through translator Antony Suzuki, "because anything that goes up, you think there's a chance. All we can do is keep the ball down and make them hit it on the ground. That's all I had in mind."
Iwakuma said his finger was fine after being bothered by a blister in his first outing against the A's. His ERA stands at 2.57 heading into his next start, which likely will be against fellow Japanese standout Yu Darvish of the Rangers on Friday at Safeco Field.
"Kuma was good again today," said Mariners manager Eric Wedge. "For him to go eight innings this early in the season says a great deal. He was very efficient. You're going to have some long balls here, but he did a nice job of controlling the baseball game, using all of his pitches. He did a nice job."
Iwakuma matched his career high with the eight innings and his ERA now stands at 2.64 in 18 starts since moving into the Mariners rotation in midseason last year.
"You tip your hat to him," said White Sox skipper Robin Ventura. "He was moving it around and he has a little bit of a funky delivery. He gave up the homer in the first, after that he was pretty sharp. He was painting both sides and wasn't giving you a lot of opportunities. We didn't have many chances after the first inning."
The Mariners scored three runs in seven innings off Sale, with Morse driving his fifth home run to left field for a 2-0 run lead in the first after Jason Bay had walked. Morse's five home runs in the first week are just shy of Ken Griffey Jr.'s best start in 1997 when he had five long balls in the first five games.
Morales then hit his first homer in the sixth, a solo shot for a 3-2 lead.
But the White Sox matched the Mariners both times and then won it in the 10th in what was a familiar finish for Seattle. It was the sixth straight one-run game between the two teams, with the White Sox winning five.
The Mariners are 5-26 against the White Sox since 2010, including a 3-16 mark at U.S. Cellular.