In the early 1990s, Scharpling was the publisher of 18 Wheeler fanzine, and ran an independent record label of the same name. The first 7-inch single by Portastatic was released by Scharpling’s label in 1992. He also contributed the liner notes for The Electrifying Conclusion, Guided By Voices’s DVD documentary of their “final” live show in Chicago.

Scharpling hosted the first episode of The Best Show on WFMU on October 10, 2000. The program was a three-hour comedy, music, call-in and talk radio program that aired Tuesday nights; the program featured a roster of misfit callers (some genuine, some acting in character), along with the occasional celebrity guest. Scharpling made no money from the station, and regularly encouraged fans to donate to the non-profit station by offering elaborate pledge drive gifts.

Scharpling is considered by some as the “Godfather Of Podcasting”. Episodes of The Best Show were archived from the shows beginning, as were most of the programs on WFMU, in the RealPlayer format. It began podcasting in early 2006 with the music removed from the latest shows and offered as downloadable files on the internet through the rest of its run on the station, helping it reach an even wider audience than it had already developed.

Nearly every episode of The Best Show featured an on-air collaboration with Superchunk drummer Jon Wurster. The pair met at a concert in the early 1990s, and bonded over their mutual love of Chris Elliott’s short-lived sitcom Get a Life. As Scharpling and Wurster, they have released six albums of comedy segments from The Best Show on their Stereolaffs record label. The duo rarely performs live, with one of the few exceptions to the rule being when they hosted Matador Records’ 21st Anniversary Festival at the Palms Casino in Las Vegas in October 2010.

Starting in August 2010, Scharpling has directed a number of music videos, typically for groups that he is friends with, and mostly on an extremely limited budget. The shorts usually contain a number of celebrity cameos, and are often met with positive reviews.

Scharpling is a regular columnist for and co-founder of the sports website The Classical. He has worked as a headline contributor for The Onion, as well as the writer of Harp Magazine’s “(Not So) Great Moments in Rock” column. He has also contributed basketball-themed writing to GQ and SLAM Magazine. In 2011, Scharpling was commissioned by New York Magazine to write multi-page recaps for every episode of the fourth season of NBC’s Celebrity Apprentice.

In 2012, Scharpling directed a video for Aimee Mann’s song “Labrador”. The video begins with a brief “making of” clip in which the role of “Tom Scharpling” is played by Jon Hamm, who talks about his idea to have the video be a shot-by-shot remake of the video for the ‘Til Tuesday song “Voices Carry”. Mann states she was tricked into the video concept and is only doing this video because she is contractually bound to do so. The actual video begins, and it is a shot by shot remake of the 1985 video, with Jon Wurster in the role of Aimee Mann’s abusive yuppie boyfriend, and Ted Leo as the guitarist in Aimee Mann’s band.

On October 29, 2013, Scharpling announced that the final Best Show on WFMU was to air on December 17, 2013.

On October 10, 2014, 14 years to the day after The Best Show first aired, Scharpling announced via his Twitter page that The Best Show would return in November 2014. On December 17, 2014, the first episode of The Best Show in its new format, a web-cast and podcast, aired via thebestshow.net. The live webcast of the show follows the same format as it did on WFMU, with callers, skits performed by Scharpling and Wurster, and a three-hour run-time.

On January 18, 2019, it was announced that Scharpling would be writing a memoir for Abrams Press.