The 38-year-old Argentine striker, who starred for Barcelona and led his homeland to the 2022 World Cup, set up Spaniard Jordi Alba's goal in the 12th minute.
Then the two switched it up 29 minutes later.
Messie scored off Alba's assist in the 41st to give Miami a 2-0 halftime lead in the grudge-match contest.
American Ian Fray added a Miami goal in the 52nd minute for a 3-0 edge before Mexican midfielder Obed Vargas pulled one back for Seattle in the 69th with a ridiculous header.
The Sounders had routed Miami 3-0 on August 31st in Seattle in a Leagues Cup final that ended with a benches-clearing brawl and Inter striker Luis Suarez spitting on a Sounders staff member.
"It was important, beyond having good feelings, to find ourselves with the victory against a great rival that took away the possibility of winning a competition a couple of weeks ago," Miami coach Javier Mascherano said.
"We understood it in the best way. We played the game we had to play."
Suarez, who apologized two weeks ago, was banned from the 2026 Leagues Cup and issued a three-match ban by MLS for his actions. The Uruguayan served his second match of the suspension in the home rematch with Seattle.
Inter Miami had slid to eighth place in the Eastern Conference with a 3-0 loss at Charlotte on Saturday. But by beating Seattle, they improved to 14-6 with seven drawn for 49 points, leaping into fifth in the East and only eight points adrift of pace-setter Philadelphia with three matches in hand.
"We have seven finals left and our goal is to win all seven to finish first in the conference," Mascherano said.
"It makes the expectations with us high, invites us to be competitive, always have our guard up and not relax."
The Sounders fell to 12-8 with nine drawn for 45 points to stand fourth in the Western Conference, just one point ahead of Los Angeles FC.