Mark Russell was born Mark Ruslander (he changed his name for stage purposes) and grew up in Buffalo, New York where he graduated from Canisius High School. After high school, his family moved briefly to Florida, then moved to Washington, D.C., where he enrolled at George Washington University, but stayed for only a month. He then joined the Marines.
Russell is known for his series of PBS specials, aired live at least four times a year between 1975 and 2004. His comedy specials were a mix of political stand-up comedy covering current events and musical parodies, in which Russell accompanied himself on his trademark American flag themed piano. Russell's song parodies use melodies from old standards with new humorous lyrics pertinent to the subject matter. For example, in 1990, following the execution of Romanian dictator Nicolae Ceauşescu, Russell did a parody song on his show to the tune of "Chattanooga Choo-Choo." ("Pardon me, boys / Are you the cats who shot Ceauşescu / You made my day / The way you blew him away.") Russell himself admits that most of his jokes and songs are very topical and have "a shelf life shorter than cottage cheese."
While Russell's humor is known for skewering Democrats and Republicans alike, his humorous tirades have also poked fun at third party, independent politicians and other prominent political (and sometimes non-political) figures.
Russell has often been asked the question, "Do you have any writers?" His standard response is "Oh, yes. I have 535 writers. 100 in the Senate and 435 in the House of Representatives!" When asked if his views on current events are too caustic, Russell replies, "I follow the old newsman's adage. As they say, 'I don't make the news. I just report it.' And in my case, I don't even make the jokes. I just report them as they masquerade as news."
For several years, on the Sunday before Labor Day, Russell has made an annual appearance on the NBC news program Meet the Press, which was hosted from 1991–2008 by Tim Russert, also a Canisius High graduate.
Beginning in the early 1960s he was a regular entertainer at the Shoreham Hotel in Washington, D.C. He gained national recognition with a series of comedy albums during the Watergate scandal, and did his first public television show in 1975. From 1979 to 1984, he was a semi-regular host on the reality TV show, Real People.
In 1994, Russell found himself unexpectedly allied with the rap group 2 Live Crew, when the group was sued for copyright infringement for their parody of the song "Oh, Pretty Woman". The case went to the Supreme Court, where Russell and the members of 2 Live Crew argued that song parodies were protected under fair use. The Supreme Court agreed, and ruled in favor of Russell and 2 Live Crew (Campbell v. Acuff-Rose Music, Inc.).
In 2010, Russell announced his retirement from public performances and made his last public performance July 2010 in Chautauqua, New York. He continues to write political humor for various venues. 
By 2013, Russell had begun to tour and perform publicly again.