Propositions B and C addressed plans for 8 Washington, a proposed 134-unit condo complex located in the city's Financial District north of the Ferry Building.
According to unofficial results as of 10:20 p.m., voters rejected Proposition B by a 62 to 38 percent margin, while Proposition C lost with 67 percent of city residents voting no.
The city's Board of Supervisors last year approved increasing the maximum height allowed for buildings on the lot to make way for the 8 Washington project, but opponents gathered tens of thousands of signatures to put the plans on hold and put a referendum on the ballot in the form of Proposition C.
The project's supporters put a competing measure on the ballot as Proposition B.
Opponents called the project a "wall on the waterfront" that would make the area inaccessible to the public.
Proponents including Mayor Ed Lee and Lt. Gov. Gavin Newsom said the project would create 30,000 square feet of new public open space on a site that currently has an asphalt lot and a private club blocked off by a 1,735-foot-long fence.
Jon Golinger, a spokesman for the opponents, called the results a "resounding rejection of the Lee administration's way of doing business on our waterfront."
Golinger said the project was "rubber-stamped" by city officials but voters were clear that "they didn't like what they saw."
David Beltran, a spokesman for 8 Washington's proponents, was not immediately available to comment on the results.
There were only two other measures on San Francisco's ballot -- 69 percent of voters approved Proposition A, which protects the recently implemented Retiree Health Care Trust Fund from being used by the city for other budgetary needs.
Proposition D, which called on the city to use all available resources to reduce its costs for prescription drugs, also passed with the approval of 80 percent of voters.
All four measures on San Francisco's ballot needed only majority approval to pass.