[2][3] He is the son of Katherine "Kay" Border and Jay G. Sykes,[4] a lawyer who later worked as a journalist for several small newspapers in New York before joining the Milwaukee Sentinel in 1962.

[2] While at Milwaukee, Sykes was a member of the Young Democrats of America, and following a nonreligious upbringing he converted to Roman Catholicism at age 18.

In 1974, using the slogan "A Different Kind of Democrat" due to his opposition to abortion, Sykes challenged Republican incumbent Jim Sensenbrenner for Wisconsin State Assembly and lost.

"[2] Sykes began his career as a journalist, starting in 1975 with West Allis, Wisconsin, weekly The Northeast Post for a year.

He made his book debut in 1988 with Profscam: Professors and the Demise of Higher Education, inspired by his father's essay published posthumously in the October 1985 Milwaukee Magazine recalling his experience teaching at the University of Wisconsin–Milwaukee.

[2][11] In 2002, Sykes and fellow WTMJ host Jeff Wagner gained prominence in leading a campaign to recall Milwaukee County Executive Tom Ament, who was embroiled in scandal for changing the county pension policy to give himself and close aides large payouts; Ament controversially retired at the end of February 2002, rather than resign, to retain his pension.

[12][13] In a 2005 speech, Jay Heck, executive director of the Wisconsin branch of the liberal political advocacy group Common Cause, referred to Sykes' influence on local politicians.

"[14] Sykes opposed the 2016 presidential campaign of Donald Trump, campaiged against him and cast a write-in vote for independent conservative candidate Evan McMullin.

[18] In December 2016, Sykes wrote an op-ed for The New York Times suggesting that the conservative movement had lost its way during the 2016 campaign, saying that "as we learned this year, we had succeeded in persuading our audiences to ignore and discount any information from the mainstream media.

[26][27] As early as 1996, rumors had circulated of a relationship between Sykes and Janet Riordan, an opera singer and author seven years his junior.