Hernandez, coming off his first loss in 10 decisions, had his consecutive quality-start streak end at a club-record 18, the third-longest in the Major Leagues since 2000.
Only Chris Carpenter of the Cardinals, who had 22 in 2005, and Johan Santana, 21 for the Twins in '04, had longer streaks of three or fewer runs in at least six innings.
Seattle (11-13) lost for the sixth time in eight games and fell into last place in the AL West.
The beginning of the end for Felix came with two outs and two on in the second inning.
A run already had scored, but the inning appeared to be over when a popup that sailed over shortstop Jack Wilson's head dropped between left fielder Milton Bradley and center fielder Franklin Gutierrez, allowing both runners to score.
"[Bradley] misread it," Wakamatsu said. "He thought Guti had it covered in the left-center gap."
Bradley said that he didn't realize Gutierrez was shading Andrus to hit the ball the other way.
"I saw it completely," Bradley said. "I didn't pick up Guti before the pitch because I automatically thought he was standing right there. But he shifted over [towards right field], and the ball landed in. I looked up, and he was looking at me. I was like, 'Oh, shoot.'
"I'm out there trying to catch everything. It was just one of those plays. If you want to blame me, I'll take the blame. I'm used to that."
Wakamatsu admitted that the miscue hurt, but he also bemoaned his club's missed offensive opportunities.
"It was a mistake and cost us early," Wakamatsu said, "but it goes back to our offense."
After Seattle was shut out for 12 innings on Friday night, the three-run deficit loomed large. It did not boost confidence when the Mariners loaded the bases with one out in the second inning off Rangers starter Matt Harrison, only to have catcher Rob Johnson bounce into a double play.
The Mariners snapped a 15-inning scoreless streak in the next inning on Jose Lopez's two-out single to left field. Lopez's second hit of the game scored Wilson, who reached on a leadoff single, and went to second on an infield out.
Bradley cut the deficit to one run with a swinging-bunt single to third.
But the Rangers retaliated in the fifth inning off Hernandez, beginning with Josh Hamilton's opposite-field home run to left field. Hernandez walked the next two batters and was replaced by reliever Jesus Colome.
It was the earliest departure for Hernandez since May 9, 2009, against the Twins.
The staff ace said his back began to tighten up in the third inning while pitching to Ian Kinsler, who eventually walked.
"I'm the kind of guy, I don't like to say nothing," Hernandez said. "I'm going to go out there and just battle. It was not my day today. My pitching was all right, but it was not my day."
The discomfort got so bad that he had treatment between innings, something that he said never had happened to him prior to Saturday.
"He just didn't have the finish on pitches that he normally has," Johnson said. "Usually, within the last five to ten feet, his stuff is moving in every direction. He didn't have that today.
"It just didn't look like Felix out there. Usually, when Felix is on the mound, it's like a train is coming at home plate. It didn't feel like that."
Hernandez assured everyone that his back would be fine and he'll make his next start, scheduled for Friday night against the Angels at Safeco.
"I'll be ready for the next one, that's all."
Wakamatsu said Hernandez's difficulties were obvious.
"You are watching him out there, and his command wasn't there," he said. "His changeup wasn't quite as sharp. He walked around, taking more time out there, but about the third or fourth inning, he had to come in and have it adjusted. At that point, we knew he wasn't right.
"I don't think it is long term or serious."
The same might not be said of the Mariners' offense.
"We had opportunities in the second inning, with the bases loaded, and again in the eighth and ninth," Wakamatsu said. "It goes back to runners in scoring position. We were 3-for-15. Guys are pressing right now. We will go out and keep working on the problems we are having right now.
"It's an offensive issue right now, and it's something we have to address."
The Rangers have now won the first two games of the series and are 4-1 against Seattle this season.
Rangers manager Ron Washington referred to the fly ball that did not end the top of the second inning as the game-changer.
"When that ball fell in, and we got those two runs, it might have affected him," he said of Hernandez. "Felix wasn't at his best, but we made him throw some pitches. The reason why he exited early was because we got his pitch count up."