The Trinidad & Tobago international tore the anterior cruciate ligament in his left knee during a 2-1 away win against his former club Orlando City on Saturday.
Molino previously tore the ACL in his right knee in May 2015 while playing for Orlando in a friendly against Brazilian side Ponte Preta. He returned to record 11 goals and eight assists for Orlando in 2016, finishing as a finalist for MLS Comeback Player of the Year honors.
The 27-year-old had been off to a strong start to the 2018 campaign, with two goals and an assist through two games.
Molino has notched 20 goals and 19 assists in 69 MLS matches since entering the league in 2015. He also has 19 goals in 43 caps for Trinidad & Tobago.
Minnesota confirmed in a news release that Molino is not expected to return in 2018, with the injury typically requiring a recovery of six to nine months.