She graduated in 1994 from The Evergreen State College in Olympia, Washington.

Kelso started working in the 1990s, with the minicomic Girlhero, which won her a Xeric Foundation grant in 1993. She has since published several other projects including Queen of the Black Black and The Squirrel Mother. She was the editor of the female cartoonist anthology, Scherherazade: Stories of Love, Treachery, Mothers, and Monsters (published by Soft Skull Press). Among many other publications, Kelso had a story (which she co-created with Ron Rege) in SPX 2004.

She received two Ignatz Awards in 2002, for Outstanding Artist (for Artichoke Tales #1 and her story in Non #5) and Outstanding Minicomic (for Artichoke Tales #1).

From April 1 to September 9, 2007, Kelso published a weekly comic strip in The New York Times Magazine titled Watergate Sue. She is currently completing her Artichoke Tales graphic novel for Fantagraphics Books.

Kelso has also created work for several magazines, including the now-defunct Tower Records' Pulse Magazine.

Kelso is married and lives with her husband and daughter in Seattle, Washington.