Tampa Bay sacked Troy Smith six times, forced two turnovers, and held the 49ers to only 189 total yards of offense, in a shutout win by the score of 21-0. It was the Buccaneers first win at San Francisco since 1980, and the 49ers first home shutout since 1977. Early in the second quarter, Tampa Bay drove 80 yards in 14 plays, culminating in a 6-yard touchdown run by "Cadillac" Williams. Tampa Bay took a 7-0 lead into halftime. With 3:36 remaining in the third quarter, Josh Freeman completed a pass 33 yards to Mike Williams to the San Francisco 33-yard line. Four plays later, Freeman completed to Williams for an 8-yard touchdown pass, and a 14-0 lead. The Tampa Bay defense forced a turnover on downs, and on San Francisco's next possession, Ronde Barber intercepted Troy Smith. The turnover led to Tampa Bay's third touchdown, a 1-yard pass to offensive tackle Donald Penn. Wide receiver Mike Williams was arrested two days before the game for DUI charges, but was released on bail and played in the game.

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