Wilson notably contributed in the prosecution of Chicago mobster Al Capone in 1931, and as a federal representative in the Lindbergh kidnapping case.

[1] During World War I Wilson served for the United States Army for a brief stint before being honorably discharged in 1919 due to poor eyesight.

- Elmer L. Irey[2]"[Wilson] sweats ice water" - Suspect who was interrogated by Frank J. WilsonIn January 1929, an investigation conducted by Prohibition agents under Alexander Jamie (including Jamie's brother-in-law, Eliot Ness) into bootlegging in Chicago Heights uncovered evidence indicating that Al Capone's brother Ralph had not paid taxes on a sizable illegal income.

The 1927 Supreme Court decision in United States v. Sullivan having already established that any criminal activities that yield an income are subject to income taxes, the Intelligence Unit of the Bureau of Internal Revenue headed by Elmer L. Irey began to build tax evasion cases against leading figures in the Chicago Outfit, with the ultimate goal of convicting Al Capone.

In April 1930, their efforts resulted in Ralph Capone's conviction for tax fraud, but the Intelligence Unit still lacked enough evidence to build a case against his brother Al.[3]: 166–172, 205–207, 262–263 In March 1930, attorney Frank J. Loesch of the Chicago Crime Commission asked President Herbert Hoover to take down Al Capone, adding additional impetus to the Intelligence Unit's efforts.

Tax investigators in Chicago suspected that a large amount of Capone's income came from his interest in a race track for dogs, called the Hawthorne Kennel Club, in Cicero, run by a lawyer named E. J. O'Hare.

[3]: 241, 265–269 From the time Wilson and his agents were put on the case, they examined over 2 million documents and evidence acquired in a number of raids on Capone's establishments over a six-year period.

Wilson and his men questioned merchants, real estate agents, proprietors, hotel clerks, bartenders, and accountants, many of whom were to afraid of what might happen to them if they gave information away about Capone.

[2] In attempting to find evidence of taxable income received by Capone ally Jake Guzik, Wilson and his agents found that someone going by the name of J.C. Dunbar purchased $300,000 worth of cashier's checks at a bank in Cicero.

[2] In late 1930, O'Hare alerted the Intelligence Unit that Capone had hired killers from New York to assassinate Wilson, prosecutor George E. Q. Johnson, and other law-enforcement officials in Chicago.

[3]: 308–311 [4]: 296–297 After the Treasury Department finally got all the evidence they needed to put an end to Capone, in March and June 1931 a grand jury met in court to decide his fate.

Some sources indicate that Wilson had insisted on tracking the serial numbers on the gold certificates used as ransom money (which ultimately led to the arrest and conviction of Bruno Richard Hauptmann).

In the Brian De Palma 1987 film The Untouchables, the character Oscar Wallace (played by Charles Martin Smith) is loosely based upon Wilson.