In the 1920s, the League campaigned doggedly to institute a city manager form of municipal government. After losing the second vote on the issue by a mere 111 ballots out of 90,000 in 1926, it laid the issue to rest. The League's efforts to promote land-use planning and zoning met with more success when the City Planning Commission was established in 1924. During this decade, the League's interests touched on themes that would recur later in its history, including a proposal for a privately financed pontoon bridge across Lake Washington; creation of a tri-county Sewage Commission to combat the increasing pollution of Lake Washington and Puget Sound; and advocacy of a special property tax to subsidize the city's trolley system.

Despite hiring an energetic and ambitious young attorney named Warren G. Magnuson as its secretary in 1930, the fortunes of the Municipal League, like those of the rest of the country, plummeted with the Great Depression. Membership declined from over a thousand to barely 300. The League felt compelled to take two major steps: it hired its first full time executive secretary, Glen Fastburn and it finally voted to admit women as members. The latter proposal had been "on the table"' since 1913, but League elders repeatedly dodged the issue through many of the same sort of parliamentary maneuvers they deplored in government. On March 6, 1937, a full 17 years after women received the right to vote through constitutional amendment, the Board of the Municipal League voted 18 to 7 to admit its first female members.

Even with its depleted numbers, the disruptions of Depression at home, and war clouds abroad, the League kept busy during the 1930s. It advocated the permanent registration of voters to replace the extant system under which citizens registered anew for each election, and it continued its campaign for city-county government consolidation, improved public budgeting, and long range capital planning. In 1934, the League even dallied with promoting a political slate, endorsing "The Order of Cincinnatus" candidates who swept out the incumbent Seattle City Council in that year's election.

In the 1940s, League membership began to rebound, exceeding 1500 in 1941 through the efforts of a membership "blitzkrieg." Ewen Dingwall, who would later make his mark as director of the 1962 Century 21 World’s Fair, moved up from League editor to executive secretary. Despite the demands of World War II the League remained active, successfully arguing in 1943 for a Freeholders election to draft a new City Charter for Seattle and in 1945 for new state law mandating centralized county purchasing.

For inspiration in these times, the League’s Municipal News quoted President Woodrow Wilson: "War must not destroy civic efficiency." After the war, the League won passage of the new City Charter in 1946, which is still the city's basic law. It also advocated and won adoption in 1948 of a state law permitting “home rule” county charters, which the League argued would “unshackle" counties from the chains of Olympia and allow for more efficient government.