Wemple was raised in Niskayuna, New York, and attended Hamilton College in Clinton, New York, graduating in 1986. In 1986-87 Wemple taught and coached sports at Trinity Pawling School, in Pawling, New York. In the fall of 1987, he moved to Washington, D.C., to pursue graduate studies at Georgetown University.
Wemple began contributing articles to the Washington City Paper in the late 1990s. From January 1999 to November 2000, Wemple wrote the paper's political column, "Loose Lips", before becoming editor. Previously, he was Washington correspondent for Inside.com and CableWorld magazine.
In June 2006, Wemple accepted the editor-in-chief position at The Village Voice. A month later, he announced he would not assume the position, stating that "the paper's ownership and I have failed to come to terms in our many discussions about moving forward, particularly with respect to newsroom management."
In February 2010, Wemple informed the staff of the staff of the Washington City Paper that he was leaving to be the new editor of TBD.com.
In 2013, J. K. Trotter of Gawker Media declared Wemple a "hero", and that "like a deeply embedded anthropologist, Wemple scours Washington media (and, not infrequently, their New York counterparts) for hypocrisy, excess, and corruption. He's the anti-Mike Allen, frequently piercing the Politico's madman's self-inflating bubble of hype at the moment it threatens to blot out the sun."