O'Sullivan connected on 16-of-23 passes for 189 yards. Gore also caught four passes for 32 yards.
Delanie Walker and Isaac Bruce each grabbed a scoring pass for the 49ers (2-1).
Detroit's Jon Kitna completed 15-of-30 passes for 146 yards and a touchdown, with one interception.
Rudi Johnson carried 14 times for 83 yards and also caught three passes for 48 yards and a touchdown for Detroit (0-3).