Choo, traded to the Indians by Seattle in 2006, hit a 3-1 fastball from Doug Fister (4-11) against the right-center-field wall in the Indians' four-run sixth to score all three runners without a throw.
He added his two-run shot in the ninth to match his season-high for RBIs. Choo had five RBIs against the Chicago White Sox on April 18.
Choo leads Cleveland in home runs (16) and RBI (68).
Asdrubal Cabrera had three hits for the Indians.
Russell Branyan, traded from the Indians to the Mariners on June 26, hit his 21st home run, a two-run shot in the third.
Josh Tomlin (3-3), in jeopardy of being lifted during the Mariners' three-run third, lasted six innings to pick up the win. He allowed seven hits, three runs, struck out five and walked none.
Chris Perez worked the ninth for his 17th save in 21 opportunities.
Fister yielded a one-out single to Cabrera in the first inning then retired the next 14 batters.
In the sixth he seemingly couldn't get anyone out.
Luis Valbuena led off the inning with a single. With one out, Michael Brantley and Cabrera singled, loading the bases to set up Choo.
Fister threw 32 pitches in the inning, retiring just one batter. He has lost 10 of his last 11 decisions.
The Indians had a chance to break the game open in the seventh, loading the bases with no outs. But Garrett Olson popped up Cabrera, struck out Choo and Hafner flied out.
The Mariners collected all their runs in the third. Ichiro Suzuki stroked a one-out double into the right-center gap. He moved to third on Chone Figgins' single to left. Franklin Gutierrez had a sacrifice fly for his team-leading 52ns RBI.
Branyan then worked a count full against Tomlin before unloading with a third-deck home run to right for a 3-0 lead.
That ended a season-high seven-game homer-less streak.
Notes: Mariners manager Daren Brown admits his bias but said RHP Felix Hernandez's "name has to be mentioned any time you talk about" the Cy Young Award. Despite a 10-10 record, Hernandez is second in ERA (2.38), tied for first in strikeouts (200) and fifth in opponent average (.222). Brown likes his innings pitched numbers (first at 211.1) and quality starts (26 of 29). "You look at both of those and they tell me that every fifth day he's going out there that he's not giving you a chance to win. That really sticks out." ... 1B Matt LaPorta has had just one plate appearance since injuring his right hip Sunday. "The training staff doesn't think he's ready to be on the field just yet," Indians manager Manny Acta said. He said it's possible he could play Friday.