The loss drops the Rangers to four games behind the Angels in the American League West race and 2 1/2 games behind the Red Sox in the Wild Card race. It was also their first home loss to the Mariners this season.
The Rangers are 10-5 since the All-Star break.
Hunter allowed five runs -- four earned -- over five innings. He gave up three walks, hit a batter and threw a wild pitch. It was the most runs Hunter has allowed in a start this season.
He had allowed five runs over his previous five starts entering the night.
"Tommy just didn't have his location tonight," manager Ron Washington said. "They made him throw some pitches."
Ken Griffey Jr. clubbed a three-run home run in the first inning, and Hunter allowed two more runs in the third inning. He became the 400th pitcher to allow a home run to Griffey.
The Rangers had several opportunities to score some runs against Mariners starter Felix Hernandez, but couldn't convert.
"We had Hernandez on the ropes," Washington said. "It might have been different if we got a few hits early. Hernandez didn't have his [best stuff] either."
Omar Vizquel and Michael Young reached base to lead off the first inning, but David Murphy grounded out and Marlon Byrd flied out to right field. Vizquel tried to score on the play but was thrown out at the plate on a close play to end the threat.
With a runner on in the second inning, Jarrod Saltalamacchia and Elvis Andrus walked back-to-back to load the bases with two outs. Vizquel flied out to right field to end the threat.
Saltalamacchia doubled to lead off the seventh before Andrus was hit by a pitch. Vizquel struck out for the first out, but the ball bounced around catcher Rob Johnson. Saltalamacchia took a few steps off second, but Andrus ran to second. Saltalamacchia was caught in a rundown and tagged out for the second out of the inning.
Young lined out to end the inning.
"We missed opportunities in a few innings," Murphy said. "It's something we need to take advantage of when we get a chance. There's no guarantee we win, but you want to get some runs."
Nelson Cruz hit a home run for the Rangers' first run of the game. He also drove home Byrd in the sixth inning on a RBI single.
Cruz's home run went an estimated 458 feet to left-center, the fourth longest in Rangers Ballpark history. He has been on a deep-homer binge, also putting up an estimated 451-foot shot, tied for seventh on the all-time list, in Arlington on Monday.
The record is 491 feet by Paul Sorrento of Tampa Bay.
Cruz became the 21st player in Rangers history with 25 home runs in one season.
"I think the biggest thing with Felix right now is he is battling, not fatigue, but more just not feeling his release point," said Mariners manager Don Wakamatsu. "You could see it that he wasn't executing his pitches the way he wanted."
Cruz noticed Hernandez's struggles, too.
"That's what I thought after I saw him in the first inning," Cruz said when asked about Hernandez's struggle with his command. "He didn't have much control, and we didn't take advantage. We gotta get walks and make things happen."
Hernandez threw 104 pitches, 58 for strikes and 46 for balls. He allowed more walks (four) than strikeouts (two) for just the second time this season. His two strikeouts match a season low.
"I don't know how I allowed just two runs," Hernandez said. "That is hard to believe. I am disappointed with my performance today. I don't know, I just felt terrible. I was all over the place."