Santana, who signed with the White Sox on a minor league deal in February, is 0-2 with a 9.45 ERA in three starts this season.
"Frankly, we weren't quite getting what we were hoping for out of that spot in terms of consistency and we decided to make a change," general manager Rick Hahn said Friday. "We didn't feel like it was working out, and we decided to go a different direction in the interest of the long-term."
Jimenez was placed on the bereavement list Monday so he could return to the Dominican Republic following the death of his grandmother. He is hitting .231 with two doubles, three homers and eight RBIs in 20 games this season. He is batting sixth in Friday's lineup.
The 36-year-old Santana, who won 16 games for the Minnesota Twins in 2017, missed the bulk of last season after having surgery on his right middle finger in February. He was reinstated on July 25 and went 0-1 with an 8.03 ERA in 24⅔ innings over five starts with Minnesota before being shut down again with problems in the finger.
Santana was an All-Star in 2017, going 16-8 with a 3.28 ERA in 211⅔ innings over 33 starts. He led the majors with five complete games and three shutouts. He started the AL wild-card game, which the Twins lost at Yankee Stadium.
Santana, who has made 384 starts in 15 major league seasons, has a career record of 149-127 with a 4.09 ERA.