After Franklin’s sudden polio diagnosis, Eleanor Roosevelt commits to enabling his political future despite pressure from her mother-in-law, Sara. As the Watergate scandal unfolds, Betty Ford unexpectedly becomes Second Lady upon Jerry’s nomination as Vice President and she clashes with his staff over her newly public role. Following the historic 2008 election, Michelle Obama wrestles with the expectations and dangers that Barack and their children face as the first Black family to live in the White House.

Moved by the toll the Great Depression has taken on the country, Eleanor presses Franklin to act more boldly and lobbies for an unprecedented formal position in the administration while helping craft his inaugural address. After Nixon’s resignation, Jerry assumes the presidency and Betty becomes First Lady days before an important state dinner, which Jerry's staff try to cancel. In the days leading up to Barack’s inauguration, Michelle faces opposition from members of his transition team who plan to diminish her role.

Young Eleanor reluctantly cuts short her progressive education in London to make her dreaded societal debut as a member of New York’s prestigious Roosevelt family, which includes her ambitious cousin, Franklin. In Michigan, Young Betty, trapped in an abusive marriage, finds herself pursued by hotshot lawyer Jerry. As she rises the ranks at a Chicago law firm, Young Michelle gets to know an idealistic and politically inclined summer intern named Barack.

Years before first entering the White House, Eleanor discovers Franklin’s marital indiscretions, which push her to socialize with more independent, politically active women in the salons of New York City. While Jerry rises through the ranks in Congress, a stubborn shoulder injury drives Betty to seek help from a doctor, who prescribes addictive pain medication. After toddler Sasha is rushed to the hospital with meningitis, Michelle vows to hold Chicago’s inadequate healthcare system to task by working to improve it from the inside.

Frustrated by the male dominated world of media and politics, Eleanor holds the White House’s first all-female press conference and grows closer to journalist Lorena “Hick” Hickock. Betty’s public announcement of her breast cancer diagnosis shifts opinion of the Ford Administration away from Jerry’s controversial pardon of Nixon and makes Betty a popular figure among American women. After Barack gets clobbered in the midterms, Michelle launches a new healthy school lunch program, which prompts a stalled Congress to enact new legislation.

Eleanor moves Hick into an adjacent bedroom in the White House while Franklin has the FBI surveil her actions. Inspired by her growing influence and popularity, Betty steers a White House campaign office to ratify the Equal Rights Amendment, which aggravates Jerry’s staff who worry about a conservative challenge for the upcoming Republican Party presidential nomination. Michelle pushes Barack to take a firm moral stand in favor of marriage equality over his political concerns about losing re-election.

After African-American opera singer Marian Anderson is banned from performing for the Daughters of the American Revolution, Eleanor leaves the group and doubles down on her efforts to confront racism. Betty’s popularity helps Jerry secure the Republican nomination for re-election, but her growing problems with addiction threaten the family and her health. After gun violence tragedies hit both the national stage and her own childhood neighborhood, Michelle grieves with Barack and advocates for legislative action.