Obama's first stop was a private Democratic National Committee roundtable that shut down the streets near Pacific Avenue and Montgomery Street until about 4:30 p.m.
It appeared the event was held at Cotogna restaurant at 490 Pacific Ave.
A small crowd of onlookers gathered behind police blocking off the intersection, including a group of women who said they worked nearby and had waited about an hour to catch a glimpse of the first lady.
Her motorcade, headed by dozens of San Francisco police on motorcycles, eventually made its way from the restaurant down a cleared out Montgomery Street around 4:30 p.m.
Obama was taken to a reception with about 200 supporters at 1 Leidesdorff St., off of California Street between Montgomery and Sansome streets.
DNC donors and guests had lined up on Pine Street ahead of the 3 p.m. entry time, including Fremont Vice Mayor Anu Natarajan.
Natarajan said she was invited by Congressman Eric Swalwell, D-Pleasanton, and was excited to represent Fremont, which has incorporated components of Obama's "Let's Move" campaign to keep residents healthy.
Richmond resident Cynthia LeBlanc, a retired educator, said she donated to the DNC for the opportunity to meet the first lady.
"I've been trying to meet her ever since she's been in office," LeBlanc said.
She initially had tried to see her during a scheduled DNC fundraiser visit to San Francisco in October, but that trip was canceled because of the federal shutdown.
"She's a wonderful role model for all of us," LeBlanc said, adding that she appreciates the work Obama has done for military families and for reducing childhood obesity.
Naeemah Charles was attending the reception as a member of the College Democrats at San Francisco State University.
Charles, 19, is a sophomore political science major at the college, and said she admires Obama.
She described her as "so strong and intelligent" and said, "She's a lot more independent than other first ladies."
Obama is staying in San Francisco Friday for a Democratic Congressional Campaign Committee women's lunch and reception at the Fairmont Hotel.
Tickets for the event, located at 950 Mason St., have already sold out. According to an invitation on the DCCC's website, tickets went for $500 to $32,400 per person.