The 33-year-old Bryans were attempting to secure their place as the most decorated doubles team since the Open Era began in 1968. The Bryan brothers remain tied with the Australian duo of Mark Woodforde and Todd Woodbridge with 11 major titles.
Paes and Stepanek are veteran doubles players but were teaming up for just the fourth time. Before partnering for a tuneup event at Sydney earlier this month, the Indian and Czech duo hadn't played together for nearly six years.
The Bryans have captured each major at least once, but they've been most dominant at Melbourne Park, where they've won four straight Australian titles and six overall. They hadn't lost here since the quarterfinals in 2008.