The 33-year-old left-hander is the first player ejected and suspended under the league's new crackdown on pitchers using foreign substances.
Santiago is appealing the suspension, which was handed out by MLB senior vice president Michael Hill, and is eligible to play Tuesday against the Toronto Blue Jays. If the suspension stands, the Mariners will not be allowed to fill his roster spot during the ban.
Santiago became the first player to be ejected as part of Major League Baseball's new foreign-substance protocols when he was thrown out of the Mariners' 3-2 victory over the Chicago White Sox on Sunday.
Santiago later admitted he used rosin on his glove side, which is in violation of the foreign-substance rule. The glove was sent to New York, but sources said it wasn't necessary to further inspect it, as the ejection and suspension are solely based on the umpires' report of having detected a foreign substance.
"It was rosin and rosin is behind the pitcher's mound, so it's not foreign. It's not a foreign substance," Mariners manager Scott Servais told reporters Tuesday. "So I am surprised, to some degree. But I understand what Major League Baseball is trying to do, they're trying to create a level playing field and understand why they decided to do this in the middle of the season."
MLB rules state the umpire will be the "sole judge" on whether any portion of the foreign-substance rule has been violated.
The ejection occurred in the fifth inning as Santiago was being pulled from the game. As is the norm, on the way to the dugout, umpires checked him for foreign substances, and they threw him out after feeling something sticky on the inside of his glove.
Santiago started this season at Triple-A and made his big league season debut with the Mariners on June 1. He is 1-1 with a 2.65 ERA in nine games.
Servais said in his history with Santiago -- both in Seattle and with the Los Angeles Angels -- he found the pitcher to be a proponent with fellow players not to use foreign substances and to use only rosin.
"When we are doing the right thing, we're following the rule and then lo and behold something like this happens," Servais said. "Again, it is going through the appeal process and we'll wait and see where it goes from there."
The Associated Press contributed to this report.