In the 1840s, in the slave state of Maryland, we meet Araminta "Minty" Ross (Cynthia Erivo), who is bound in servitude on the Brodess farm, despite being recently married to a freedman, John Tubman (Zackary Momoh). Minty's family is fragmented; while she remains enslaved along with her mother, Harriet "Rit" Ross (Vanessa Bell Calloway) and sister, two of her siblings have already been sold off to another owner down South. Minty's father, who has the status of a freedman, attempts to negotiate her freedom with Mr. Brodess, as it was promised that Minty's mother and her family would be freed when she turned 45, a commitment made by Brodess's great-grandfather. However, despite Minty's mother being 57, Brodess dismisses the plea, asserting they are meant to remain in bondage and even destroys a letter that John had procured from a lawyer.
The situation turns dire when Gideon (Joe Alwyn), Brodess's son, witnesses Minty's fervent prayers for divine intervention against her oppressor, taunting her about the lack of care God has for the prayers of slaves. Shortly after, Brodess passes away, causing Gideon to lash out by planning to sell Minty in punishment. Plagued by debilitating visions after suffering a head injury as a child, Minty envisions her escape to freedom, and she resolves to flee.
Determined, Minty instructs John to stay behind to ensure his own safety and promises to reunite later. As she embarks on her journey, Gideon chases her to a riverbank, promising not to sell her if she returns; yet, with a defiant spirit, she leaps into the water, declaring she would rather perish than live in chains. Believed to have drowned, Minty manages to reach Philadelphia through the Underground Railroad, aided by Quakers and abolitionists. In Philadelphia, she encounters Marie Buchanon (Janelle Monáe), a stylish boarding-house owner and the daughter of a freed slave, and William Still (Leslie Odom Jr.), an influential abolitionist who inspires her to adopt a new name—she chooses Harriet, in homage to her mother.
Despite the pleas of Marie and William to remain in safety, Harriet longingly decides to return to rescue John. Upon her arrival at his homestead, she is heartbroken to learn that John has moved on, marrying and expecting a child with another woman, believing her to be dead. Undeterred, Harriet embarks on a mission to liberate her family but faces resistance when her sister hesitates to leave her children behind. Driven by her unwavering spirit, Harriet transforms into a conductor on the Underground Railroad, successfully guiding many slaves to freedom and earning the nickname “Moses” as the legend of her heroic endeavors begins to spread.
While she secures freedom for numerous family and friends, her own sister remains a prisoner of the Brodess household. William, fearing for her safety, urges her not to undertake the perilous rescue. The stakes escalate with the passing of the Fugitive Slave Act, putting escaping slaves at risk of capture even in free territories. Gideon becomes furious upon discovering Harriet's identity as Moses, with fellow slave owners demanding recompense for the losses incurred from her rescues. His pursuit of her leads him to Philadelphia, accompanied by the relentless slave hunter, Bigger Long (Omar J. Dorsey), who tragically takes Marie's life during the chase. In a bid for freedom, Harriet escapes north to Canada.
In Canada, Harriet remains unyielding, insisting that the mission of the Underground Railroad must endure. She carries on with her remarkable work, leading many more runaway slaves to safety, although heartbreaking losses occur along the way, including the death of her sister before she can be rescued. Eventually, the Brodess estate collapses into ruin as Mrs. Brodess (Jennifer Nettles) pledges to capture Harriet, using her sister's children as lures. However, in a dramatic turn, Harriet's allies overpower Gideon's family and reclaim the last of the Brodess slaves.
In a tense climax, Bigger Long meets his end while Harriet confronts Gideon, choosing to let him live as she shares with him her vision of his cause being vanquished by war.
In a poignant epilogue, it is revealed that Harriet freed over 70 slaves through the Underground Railroad and went on to serve as a Union spy during the Civil War, leading a contingent of 150 colored soldiers who orchestrated the liberation of more than 750 enslaved individuals.
