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.

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.