Asserting that independence and equal opportunity are fundamental American values, they said an action to deprive spousal H-4 visa holders the ability to continue to pursue their professional careers is antithetical to principles this country is built on.
"We urge you to consider the economic, psychological, and personal harms that rescinding the H-4 rule will cause to more than 100,000 professional women, their families, and their American communities," they said.
Ms Harris, the first Indian-origin American Senator, and Ms Gillibrand said a revocation of the H-4 rule would "disproportionately target" South Asian women.
"In 2017, 94 per cent of H-4 visa holders with work authorisation were women and 93 per cent were from India. Currently, no more than seven per cent of approximately 375,000 family and employment-based green cards issued annually can go to nationals from the same country," they said.
"As a result, over 306,000 Indian applicants and 67,000 Chinese applicants whose applications have been approved are currently in line to receive a green card. Because of the backlog, H1-B visa holders and dependent H-4 visa holders from certain countries in the US are forced to wait from 12 years to an impossible 150 years to receive green cards," they said.
In the letter, Ms Harris and Ms Gillibrand said requiring professional women to give up their careers to keep their families united will cause serious harm to their children.
Many H-1B families live in higher-cost areas such as Silicon Valley or Seattle, where having two incomes is not a luxury but a necessity.
"Rescinding the H-4 rule would create a permanent barrier to employment - including self-employment - for these women, reinforcing a harmful stereotype that women do not belong in the workplace and widening the gender equality gap," the senators wrote.