Santana, 36, was 0-2 with a 9.45 ERA in three starts for the Chicago White Sox this year. The team designated Santana for assignment last month.
Santana will report to the Mets' minor league complex in Port St. Lucie, Fla.
Santana is only two seasons removed from going 16-8 with a 3.28 ERA for the Minnesota Twins. He struck out 167 hitters in 211 1/3 innings for the Twins in 2017 and helped them to one of two AL Wild Card berths.
Santana has experience pitching in the NL East Division. He went 14-10 with a 3.95 ERA for the Atlanta Braves in 2014.
Santana has a career 149-127 record and a 4.09 ERA in 387 games.
The Mets are 24-25 this season. New York trails the Philadelphia Phillies by 4 1/2 games in the NL East Division.