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.
In Week 13, already nursing a sore left knee, Sanchez suffered a sprained PCL in his right knee in a win against the Bills. The injury forced him to miss the Week 14 game against the Buccaneers. He returned for the final three games of the season, leading the Jets to wins in Weeks 16 and 17 to help New York qualify for its first playoff berth since 2006.
In the playoffs, Sanchez led the Jets to upset wins over the Bengals and Chargers, joining Joe Flacco as the only rookie quarterbacks to win two playoff games. However, like Flacco the year before, Sanchez fell short of the Super Bowl, as the Jets lost to the Colts in the 2009 AFC Championship Game.