In his 70-year legal career, Loesch represented numerous corporate and individual clients, including several major railroads and the American Medical Association.
Loesch spent much of his career fighting organized crime in the city, particularly against the romantic image of the gangster commonly portrayed by the media of the time.
However, Loesch reportedly held considerable influence among Chicago's underworld and was apparently able to warn Capone and other Italian mobsters against further gang warfare, especially following the violence surrounding the 1928 Republican "pineapple primary."
Later in the same year, he was chief prosecutor in the murder case of Octavius C. Granady, an African American lawyer and candidate for Committeeman of the "Bloody" Twentieth Ward.
In 1929, President Herbert Hoover appointed Loesch as one of the eleven primary members of the Wickersham Commission on issues relating to law enforcement, criminal activity, police brutality, and Prohibition.