Manning, 30, filed her statement of candidacy with the Federal Election Commission on Thursday, listing an apartment in North Bethesda as her address.
She is running as a Democrat and will likely challenge two-term Sen. Ben Cardin in the primary. The state's senior senator is an overwhelming favorite to win.
Known as Bradley Manning at the time of her 2010 arrest, the former Army intelligence analyst was convicted of leaking more than 700,000 military and State Department documents to the anti-secrecy website WikiLeaks. She's been hailed as a traitor as well as a courageous hero.
Manning came out as transgender after being sentenced to 35 years in prison. President Barack Obama granted Manning clemency before leaving office last year.
The conservative media organization Red Maryland first reported Manning's intention to run.
The Associated Press was unsuccessful in reaching Manning for comment. She told The Washington Post on Saturday that she might release more information in the coming days.
Cardin spokeswoman Sue Walitsky did not directly address Manning's candidacy or anyone else's. But she told The AP that "Cardin is looking forward to a vigorous debate of the issues and a robust conversation with Maryland voters."
Manning would not be the first transgender candidate to challenge a sitting member of Congress.
Kristin Beck, a retired Navy SEAL who is transgender, failed to unseat U.S. Rep. Steny Hoyer in Maryland's Democratic Primary in 2016. Beck got 12 percent of the vote.
"It was too much for me to run for Congress," Beck said in a phone interview Saturday. "I should have run for something lower (state or local office). She might as well be running for president."
Beck said Manning is pulling a "publicity stunt."
"I totally, 100 percent disagree with everything she did," Beck said. "She's just grabbing headlines. I know what that feels like. I've been in the headlines. You get a sense that you're worthy and doing something that counts. And when you lose that, you try to do something to grab a headline."
Manning had said she wanted to expose what she considered to be the US military's disregard of the effects of war on civilians and she released information that she didn't believe would harm the US
Obama's decision to commute Manning's sentence to about seven years drew strong criticism from members of Congress and others, with Republican House Speaker Paul Ryan calling the move "just outrageous."
When Manning was released from Fort Leavenworth, Kansas, in May, she told The AP in an email that she was eager to define her future — but made no mention of politics.
"I'm figuring things out right now — which is exciting, awkward, fun, and all new for me," Manning wrote.
The Oklahoma native had planned to move to Maryland, where she has an aunt. She has been registered to vote at the apartment in North Bethesda since mid-August, according to the Maryland State Board of Elections.
Her recent move would not affect a Senate bid. To run for that office, a person must be at least 30 years old, a US citizen for nine years and an inhabitant of the state at election time, according to the Maryland State Board of Elections. A felony conviction does not appear to preclude a run.
Manning is yet to file for the primary with the state elections board, which she must do in person by Feb. 27, according to the board's website.
Cardin is also yet to file. But campaign finance reports show that his organization had nearly $2 million cash on hand in late September.