The loss left the four-time defending division champions 0-2 for the first time since 2002.
San Francisco (1-1) overcame eight sacks of J.T. O'Sullivan to beat the Seahawks for just the third time in 11 games, in the first overtime game of the 19-game series between the two teams.
O'Sullivan was 20-for-31 for 321 yards and one touchdown in the second start of his six-year career. Seattle's Patrick Kerney and rookie top pick Lawrence Jackson sacked him two times each, but the journeyman passer kept coming back.
The 49ers got the ball to start overtime. On third-and-7 from the San Francisco 23, O'Sullivan found Isaac Bruce over the much shorter Josh Wilson for 33 yards. Bruce caught four passes for 153 yards, his most since 2004, one week after O'Sullivan never even threw his way in a loss to Arizona.
O'Sullivan then threw a quick jump pass for 5 yards to Arnaz Battle on third-and-3. That set up Nedney for redemption.
San Francisco nearly won it when O'Sullivan frantically escaped a ninth sack and found Frank Gore for an improvised 17-yard completion. They set up Nedney for a 41-yard kick, but he missed wide right by a few feet, forcing overtime.
The Seahawks turned over the ball three times, two on deflected interceptions of Matt Hasselbeck. Patrick Willis returned one of those 86 yards for a touchdown. Hasselbeck, missing his top six receivers after two more injuries Sunday, was 18-for-36 for 189 yards -- the second consecutive substandard game for the three-time Pro Bowler.
After Olindo Mare kicked his third field goal, from 32 yards, to put Seattle ahead 30-27 with 7:41 left, O'Sullivan drove the Niners deep into Seahawks territory. San Francisco settled for a 28-yard field goal by Nedney that tied it with 2:42 left.
Julius Jones, whom the Seahawks turned to largely out of necessity when they sustained more injuries at wide receiver, started his first game for them with Maurice Morris hurt. He led a 15-play drive that ended with T.J. Duckett's first touchdown with Seattle, from 1 yard to tie it at 27.
Jones had 127 yards on 16 carries, his biggest rushing day since Dec. 24, 2005, for Dallas at Carolina. It was first 100-yard rushing day since Dec. 10, 2006, for the Cowboys against New Orleans. The 49ers rallied from a 17-6 hole late in the first half to take a 27-20 lead in the third quarter.
They tied it when Hasselbeck's pass to Billy McMullen, signed Wednesday and playing his first game since 2006, banged off him and cornerback Walt Harris near the 5. The deflection floated to Willis at the 14, and the 2007 Defensive Rookie of the Year weaved 86 yards with his first career interception and touchdown.
Then Ray McDonald reached up while getting blocked and batted Hasselbeck's pass into Harris' arms at the Seattle 41. Gore's subsequent 2-yard run, bouncing outside after getting hit, put San Francisco ahead.