He made his professional debut in 2013 with the DSL Giants and spent the whole season there, posting an 8–1 win–loss record with a 2.75 earned run average (ERA) and 1.11 WHIP in 13 games started.

[1] He began the season with the Charleston RiverDogs, and after pitching one game, he suffered an injury which required Tommy John surgery.

[7] He made four starts for the Yankees, pitching to a 3.00 ERA, and was optioned to the Scranton/Wilkes-Barre RailRiders of the Triple-A International League on July 2.

[12] In July 2021, Loáisiga, along with teammates Nestor Cortes, and Wandy Peralta tested positive for COVID-19, causing the Yankees to put him on the COVID-19 injured list and the MLB to postpone the game against the Boston Red Sox to the start of the second half of the season.

[20][21] Despite his performance, Loáisiga called the WBC a “really good experience,” adding that, "when you’re given this opportunity to represent your country and have the chance to participate in an event like this, I think any of us will take that.

It’s a unique opportunity... To be able to wear the uniform of your country, it means a lot.”[22] His father Stanley Loáisiga played in the Montreal Expos minor league system and his grandfather was an accomplished professional pitcher in Nicaragua.

Growing up, Jonathan idolized Dennis Martínez, a fellow Nicaraguan who won 245 games in the major leagues.