The owners are choosing between the 49ers new home in Santa Clara and Miami, which suffered a major blow when it lost public funding to improve its stadium. The winner will host Super Bowl 50 and the loser of the vote will then go against Houston to host Super Bowl 51.
"I have a very good feeling. If I could say we're on the five yard line and ready to go. I'm excited because I think we put together a fabulous bid. I think we were serious about it, we took nothing for granted," said San Francisco Mayor Ed Lee.
A three-quarters majority of the 32 owners is required on the first ballot. If neither city gets that, then a simple majority wins on the next ballot. Today's vote is expected to happen between 10:30 a.m. PT and 12:30 p.m. PT.
The 49ers' new home is scheduled to open for the 2014 season. The area hosted its only Super Bowl at Stanford Stadium in 1985.
Miami has staged 10, most recently in 2010. Only New Orleans has had as many Super Bowls.
Houston was host in 2004.
The AP has contributed to this report