Wilkie's task as Chief was to oversee the protection of important national officials, paramount of which was President William McKinley, foreign dignitaries visiting the United States, as well as combating the counterfeiting of currency.

Hazen's tenure had ended in disarray: in 1894, the Secret Service had taken on the responsibility of protecting the President, invoking the ire of the Anti-Federalist lobby; meanwhile a major counterfeiting operation had forced the government to withdraw an entire currency issue.

[2] The decision to appoint Wilkie was made by Secretary of the Treasury Lyman J. Gage, who wanted to experiment with placing a newspaper man at the head of the bureau.

Wilkie is featured prominently in the 2014 novel The Great Abraham Lincoln Pocket Watch Conspiracy, where he is portrayed as a loyal but combative subordinate to President William Howard Taft.

Stirling's Tales of the Black Chamber trilogy, an alternate history of World War II in which he remains chief of the Secret Service under a third Theodore Roosevelt administration.