Ibanez's slam came during a seven-run first inning. Yankees backup shortstop Alberto Gonzalez got the final out in the ninth inning in his first professional pitching appearance.
Every Seattle starter had at least one of its season-high 16 hits and Jesus Montero was the only starter who failed to score a run in the Mariners' best output this year.
The Mariners chased Phil Hughes after he got only two outs in the first. Trying to preserve his bullpen, Yankees manager Joe Girardi had Brett Marshall throw 108 pitches in his big league debut, then brought in Gonzalez.
Ibanez has connected three times in the first two games of his return to the ballpark in which—last year at 40 years old—he electrified crowds in late September and October with several key homers in the Yankees' run to the AL championship series.
This time, the cries of "Ra-uuul!" were replaced by boos for Hughes (2-3) when Ibanez connected for his 11th career slam. Ibanez homered again in the fifth inning off Marshall.
Kendrys Morales, Michael Morse and Michael Saunders each drove in a run in the highest-scoring first inning at the stadium that opened in 2009.
Kyle Seager added a three-run shot off Marshall in the sixth.
The first inning outburst made it easy for Japanese right-hander Hisashi Iwakuma (5-1), who came in with a 1.
Delivering dastardly breaking pitches with a motion that has a lengthy pause when he reaches the top of his high leg kick, Iwakuma kept the Yankees off-balance. He gave up a season-high eight hits and two runs without walking a batter for the second straight start. Iwakuma struck out four.
After getting Saunders to lead off the game with a fly to left field on the second pitch of the game, nothing was easy for Hughes in the shortest start of his career.
Dustin Ackley walked and Seager singled before Morales had an RBI single. Morse followed with another RBI hit before Hughes walked Justin Smoak to load the bases ahead of Ibanez.
Former Yankees prospect Montero singled and, after a forceout, Saunders, the 10th batter of the inning, doubled in a run to make it 7-0 and chase Hughes. The right-hander never failed to make it out of the first in his 110 previous starts.
Ibanez hit an opposite-field drive to left field in the fifth and Seager's long ball came in the sixth to make it 12-2. The Yankees bullpen remained empty, leaving it up to Marshall to pitch deep into the game.
With a chance for his first career three-homer game, Ibanez popped out foul in the sixth to David Adams, another Yankees player making his big league debut—on his 26th birthday.
Ibanez flied out in the eighth. He has 17 career mulithomer games. His previous came in the Bronx against Oakland on Sept. 22 for the Yankees against Oakland.
Gonzalez, acquired last week from the Chicago Cubs, moved from shortstop to the mound with two outs in the ninth and runners on first and third. He retired Robert Andino on a routine flyball.
NOTES: Adams got his first career hit in the sixth. ... Mariners manager Eric Wedge said LHP Felix Hernandez was "pretty sore this morning" but the ace should be fine after tweaking his back Tuesday night. Wedge said he doesn't think there will be any alteration of his routine between starts. ... Seattle OF Franklin Gutierrez (strained right hamstring) ran Tuesday and could begin a rehab assignment Thursday or Friday. ... The Yankees designated 3B Chris Nelson for assignment.