[1][2] After several years as a stand-up comedian, Spade rose to prominence as a writer and cast member on the NBC sketch comedy series Saturday Night Live from 1990 to 1996.

Following his departure from SNL, he began an acting career in both film and television, starring or co-starring in the films Tommy Boy (1995), Black Sheep (1996), Senseless (1998), Joe Dirt (2001), Dickie Roberts: Former Child Star (2003), The Benchwarmers (2006), Grown Ups (2010) and its 2013 sequel, The Ridiculous 6 (2015), The Do-Over (2016), and The Wrong Missy (2020).

He provided voice roles such as Ranger Frank in The Rugrats Movie (1998), Kuzco in Disney's The Emperor's New Groove (2000) and its direct-to-video sequel, Kronk's New Groove (2005), the red panda Aliur in Snowflake, the White Gorilla (2013) and Griffin the Invisible Man in the Hotel Transylvania film series (2012–2022).

[9] Spade attended Saguaro High School and later Scottsdale Community College before transferring to Arizona State University and dropping out shortly thereafter since he was making a decent living doing stand-up.

Some of them include a flight attendant for "Total Bastard Airlines" who bids a dismissive "Buh-Bye" to each passenger upon disembarking; a receptionist for Dick Clark who, as a matter of policy, asks people indiscriminately, "And you are?

[16] Spade wrote in his 2015 memoir that he received an angry phone call from Murphy two days later at the SNL offices; the two did not reconcile until a chance meeting in 2011.

[19] Spade starred with fellow Saturday Night Live cast member Chris Farley in two buddy comedy films, Tommy Boy (1995) and Black Sheep (1996), both of which were distributed by Paramount Pictures.

[20] Although he received several offers to star in his own TV shows, he turned them down and joined the ensemble cast of Steven Levitan's office sitcom Just Shoot Me!, opposite Laura San Giacomo and George Segal, which ran for seven seasons from 1997 to 2003.

While appearing on Just Shoot Me, Spade had his first solo starring role as the title character in the 2001 film Joe Dirt, which was a modest box office success.

From 2002 to 2006, Spade regularly appeared in commercials for Capital One (with Nate Torrence) where he played the employee of a fictional rival company whose policy toward honoring credit card rewards (and just about everything else) is "always no".

In 2004, he joined the cast of 8 Simple Rules, following the death of the sitcom's star, John Ritter, for the show's third and final season.

[27] In 2022, Spade began co-hosting the Fly on the Wall podcast with fellow Saturday Night Live alum Dana Carvey.

[34] On April 1, 2012, Spade received a Razzie Award for Worst Supporting Actress for his role as Monica (drag) in the 2011 film Jack and Jill.

Spade has dated numerous actresses and celebrities, including Heather Locklear, Lara Flynn Boyle, Julie Bowen, Teri Hatcher, and Naya Rivera,[35][36] with E!

In an interview with Howard Stern, Spade stated that he managed to get away from the 350-pound (160 kg) Malloy, run to his bedroom, grab his gun and defend himself by locking himself in a bathroom armed with the shotgun.

Malloy pleaded guilty and avoided jail time on condition that he seek counseling for drug and psychological problems.

He subsequently received five years' probation, was ordered to stay at least 100 yards away from Spade, and was required by the court to perform 480 hours of community service.

[41][42][43] In December 2005, Spade donated $100,000 to the Phoenix Police Department to buy 300 firearms, including 50 AR-15 rifles for its patrol officers.