Jost has been a staff writer for the NBC sketch comedy series Saturday Night Live since 2005, and co-anchor of Weekend Update since 2014.

[9][10][11] His mother, Kerry J. Kelly, was the chief medical officer for the New York City Fire Department,[12] and his father, Daniel A. Jost, was a teacher at Staten Island Technical High School.

[13][14] He has one younger brother, Casey Jost, a writer and a producer of Impractical Jokers; he also had a role in Staten Island Summer.

[21] Jost broke Meyers' record for being the longest-serving anchor in the history of the segment with the October 23, 2021, episode hosted by Jason Sudeikis.

[9] In addition to Weekend Update, Jost made a brief cameo appearance as Ohio Governor John Kasich in a Republican presidential debate sketch.

[32] In late 2018, Jost and Green Bay Packers quarterback Aaron Rodgers appeared in an advertising campaign for Izod.

[34] Jost, along with Michael Che, appeared on the March 4, 2019, episode of WWE's Monday Night Raw, where both were announced as special correspondents for WrestleMania 35.

In the March 4 episode, they got involved in a storyline with wrestler Braun Strowman, which resulted in both Jost and Che becoming participants in the André the Giant Memorial Battle Royal at WrestleMania.

Jost attempted to calm the situation by using his therapist, but Strowman chokeslammed him and eliminated the two comedians in quick succession, winning the battle royal.

[39] On April 27, 2024, Jost hosted the White House Correspondents' Dinner, an annual gathering of reporters usually entertained by the president and a comedian.

[54] In 2023, Jost, along with fellow SNL comedian Pete Davidson, purchased a decommissioned Staten Island Ferry boat.