Sanchez saw more action in 2007, thanks to an injury to Booty. He made three starts, beating Arizona and Notre Dame before losing to Oregon. Against Arizona he threw for 130 yards, a TD and two interceptions. The next week against Notre Dame he threw for 235 yards and four touchdowns. He had 277 yards passing and two touchdowns against Oregon, but also threw a pair of interceptions in the loss. He finished the season with 695 passing yards, seven touchdowns and five interceptions.
Sanchez beat out Arkansas transfer Mitch Mustain and redshirt freshman Aaron Corp for the starting job in spring practice in 2008. However, in the first week of fall practice, Sanchez suffered a dislocated kneecap that jeopardized his starting status. He missed three weeks of practice, but returned in time for the regular season opener against Virginia. Sanchez threw for a career-best 338 yards in that game, including three touchdowns. He had at least three TD passes in each of USC's first four games of the season, including a loss to Oregon State. Sanchez capped off his season with an MVP performance against Penn State in the Rose Bowl, throwing for 413 yards and four touchdowns. Sanchez finished the season with 3,207 passing yards and 34 touchdowns, both of which led the Pac-10. He was a first team All-Pac-10 selection and earned honorable mention All-America honors from Sports Illustrated.
After the first two preseason games, Sanchez was named the Jets starting quarterback for the 2009 regular-season opener at Houston. He became the first rookie QB to start Week 1 for the Jets since their inaugural season in 1960. Sanchez led the Jets to a win over the Texans in his NFL debut, throwing for 272 yards and a touchdown.
Sanchez led the Jets to a 3-0 start in 2009, becoming the first rookie quarterback since the AFL-NFL merger to start and win his team's first three games of the season, and earning offensive Rookie of the Month honors for September. However, he threw eight interceptions in the next three games combined, as the Jets fell to 3-3.
Sanchez helped stop the Jets losing streak, leading them to a 38-0 win at Oakland. However, during that game, Sanchez was seen eating a hot dog on the sidelines. He eventually apologized for doing so.
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