Members of the California Media Workers Guild voted 10-1 to approve concessions, including at least 150 job cuts and the removal of some benefits and rights.
Frank Vega, Chronicle publisher, said: "This agreement is critical to ensuring the survival of The Chronicle. I appreciate the willingness of our employees to work with us to make the difficult decisions that need to be made during these difficult times."
In 2008 the 144-year old paper lost more than $50m and is expected to lose even more this year. It has been losing money since 2001.
Of the Chronicle's 366 employees who are represented by the Guild 333 voted in favour of the contract concessions and 33 voted against.
As part of the agreement, workers at the paper can now be laid off "without regard to seniority", holiday allowance will be cut from four to three weeks a year, the working week will increase from 37.5 hours to 40 hours for no more pay and the cost of health benefits will increase.
Hearst, which is based in New York, has also said it may be forced to close the print edition of the Seattle Post-Intelligencer. The company is expected to make a decision this week about whether to move the paper online with a smaller staff, or close it altogether.
Speculation is that the paper will print its final edition this week and continue as a web only publication. In January Hearst revealed it was considering closing the paper, which has a circulation of 127,500, if it could not find a buyer in 60 days.
A small team of younger staff at the paper with experience of blogs and breaking news has been working on a possible digital offering.
It the Seattle Post-Intelligencer closes it would leave the city with only it's bigger rival The Seattle Times. However, the family-owned Times is also said to be heavily in debt and struggling to cut expenses.
Recent blog coverage of the US newspaper crises on BR