The plot follows Will and Hand, two childhood friends who set out on a week-long around-the-world odyssey, ostensibly to give away a large sum of money.

Shortly after receiving the sum, Will and Hand's mutual childhood friend, Jack, was involved in a car accident.

As a result of his confusion due to a conglomerate of issues, such as the large sum of money, Jack's death, Will's beating, and other personal issues, Will and Hand plan to travel around the world, visiting obscure countries and giving away all the money, bit by bit, to people they arbitrarily decide are most deserving.

One plan involves taping money to a donkey in a graph paper pouch that reads "HERE I AM ROCK YOU LIKE A HURRICANE" and another creating a treasure map for Estonian children.

However, their quest proves surprisingly tricky without a solid set of criteria or a definitive direction in their plan.

A pseudo-sequel, titled The Only Meaning of the Oil-Wet Water, follows Hand and the minor character Pilar in Central America.

In February 2003, Eggers and McSweeney's published Sacrament, a retitled hardcover edition of You Shall Know Our Velocity that included a new 49-page section inserted into the middle of the story.

Instead, he is a metaphorical representation of Will's mother, a device Will used to cope with the loss that occurred several years before the trip (rather than alive and in contact with Will as in his version).