In 1891, he moved to Chicago to work for The Chicago Herald. He covered baseball, including longtime Chicago captain-manager Cap Anson, whom he sometimes referred to in print as “Grampa.” He also covered the 1892 Republican National Convention and the 1892 Illinois legislative session. Whitlock joined the Whitechapel Club.

Whitlock had married Susan Brainerd in 1892, but she died four months after their wedding. In 1895 he married again, choosing her sister Nell Brainerd.

In 1893, Whitlock prepared the pardon documents for the Haymarket Affair’s convicted men: Fielden, Neebe, and Schwab. After Gov. Altgeld signed the pardons, Whitlock commented, “The storm will break now,” to which the governor replied, “It was merely doing right.”

His political writing attracted attention by Illinois politicians, and Whitlock was offered a job as Gov. John Peter Altgeld’s personal secretary; instead he took a position with the Secretary of State. While in Springfield, he also studied the law under Senator J. M. Palmer; he was admitted to the bar in 1894, at the age of 25.

Whitlock became very active in Illinois Democratic Party politics. In 1894, he was Chair of the Democratic Finance Committee and in charge of arrangements for the state convention.

After the defeat of Gov. Altgeld in 1896, Whitlock returned to Toledo in 1897, where he established a successful legal practice. Whitlock provided legal services to the Mayor of Toledo, Samuel M. Jones, a.k.a. “Golden Rule” Jones. In one case, Whitlock successfully argued to overturn the Ohio state statutes that governed municipalities.

Whitlock entered politics more directly in Toledo, running on the Independent ticket for mayor; he was elected four times from 1906 to 1914. He was one of a number of Progressive politicians elected as mayors of major Midwestern cities in 1911. He declined a fifth nomination as mayor when recruited for a diplomatic post.

After finishing his last term as mayor, in 1913 Whitlock was appointed minister to Belgium by President Wilson. When the First World War broke out, his responsibilities were increased as he was given representation for seven additional countries in wartime. His position was extremely sensitive after the German occupation of Belgium. His adroit performance of his duties in the office won him an international reputation for tact, zeal, and efficiency. Whitlock ensured food aid sent by the Committee for Relief in Belgium went to Belgian citizens rather than the German occupation forces.

With the United States’ declaration of war against Germany in April 1917, Whitlock needed to leave Belgium. He insisted on ensuring he accompanied other Americans out of Belgium, and crossed into Switzerland, which was neutral. During the war, he visited King Albert of Belgium at the Allied battle front.

After the signing of the armistice in November 1918 and the restoration of the Belgian government, Whitlock returned to Brussels as minister. In 1919, he went to the United States for a visit. While he was at home, the United States’ representation in Belgium was raised to rank of an embassy, and Whitlock became an ambassador.