 Weddle made his NFL regular season debut in the season-opener against the Chicago Bears and recorded three solo tackles and made his first NFL sack on quarterback Rex Grossman in a 14–3 victory.On October 28, 2007, Weddle recorded five combined tackles, broke up a pass, and made his first NFL interception in a 35–10 victory against the Houston Texans in Week 8.He made his interception off a pass attempt by quarterback Matt Schaub in the third quarter.