[11] Jacobs ran as a Democrat in the 2018 elections for the United States House of Representatives in California's 49th congressional district.

[12] A Super PAC affiliated with EMILY's List launched a media blitz right before the primary after Jacobs's grandfather donated $250,000 to the organization.

[14] She finished first in the top-two primary, and defeated San Diego City Council President Georgette Gómez in the November general election.

In 2022, Jacobs authored legislation to regulate the collection of personal reproductive health data, as in period-tracking apps.

[23][24] Along with 16 other members of Congress, Jacobs was arrested at a demonstration in support of abortion rights outside the United States Supreme Court Building on July 19, 2022.

[25][26] In 2022, Jacobs introduced a bill to rename the Andrew Jackson Post Office in Rolando after her predecessor Susan A.

She wants to hold businesses and individuals accountable for price gouging related to personal protective equipment and health care supplies during the pandemic.

[41] On April 5, 2024 Jacobs joined 39 Democrats in a call for Biden to stop the transfer of US weapons to Israel during the Israel-Hamas war in Gaza.

Jacobs signed a letter with Nancy Pelosi and including Representatives Cori Bush, Barbara Lee, Jamaal Bowman, Ilhan Omar, Rashida Tlaib and Alexandria Ocasio-Cortez.

[44] Jacobs supports including a provision to grant citizenship for undocumented immigrants residing in the U.S., and passing the DREAM Act.

[45] In March 2023, Jacobs was among 56 Democrats to vote in favor of a resolution which directed President Joe Biden to withdraw U.S. troops from Syria within 180 days.

[49] On November 18, 2023, Jacobs called for a ceasefire in the Israel–Hamas war and an end to Israel's blockade of the Gaza Strip, saying "It is time for a bilateral ceasefire — to immediately release the hostages; to establish humanitarian access and allow fuel, food, water and medical care into Gaza; and to end the bombardment of millions of Palestinian civilians.