Darnold made the expected announcement in an Instagram video Wednesday.
"I've been blessed that my life has been full of memorable moments and wonderful people," Darnold said.
About 25 minutes before Darnold's announcement, UCLA quarterback Josh Rosen also announced he will enter the draft, bringing an end to a two-year era of remarkable quarterback play at two schools about 12 miles apart in Los Angeles. Both local products are expected to be high first-round selections in April.
Darnold took over as the Trojans' starting quarterback four games into last season as a redshirt freshman and immediately became one of the most exciting players in college football.
He won nine consecutive games as a starter last season, including a thrilling 52-49 Rose Bowl victory over Penn State with a record 453-yard, five-touchdown performance.
Although he struggled with fumbles and interceptions this season, he still led the Trojans to their first Pac-12 championship since 2008. Ohio State beat USC 24-7 in the Cotton Bowl last week in a quiet farewell for Darnold, who passed for 356 yards but also lost two fumbles to give him an FBS-leading 22 turnovers this season.
Darnold passed for 7,229 yards with 57 touchdown passes and 22 interceptions in just 27 games behind center for the Trojans, going 20-4 as a starter.
In his announcement video, the quarterback praised USC coach Clay Helton, who was the Trojans' quarterbacks coach when Darnold arrived on campus in 2015 before taking over as head coach during that redshirt season. Helton promoted Darnold to the starting job over touted recruit Max Browne early last season.
"I cannot thank you enough for believing in a kid from San Clemente High School with such little game tape, and for giving me the opportunity and chance to start at such an incredible university," Darnold said.
Darnold and Rosen grew up on opposite sides of the Los Angeles area's sprawling suburbs, and now they'll be linked as top quarterback prospects in the same draft.
Darnold's Trojans beat Rosen's Bruins 28-23 for the Victory Bell on Nov. 18 in the local products' only collegiate game against each other. Darnold redshirted the 2015 season, and Rosen was injured for the crosstown showdown in 2016.
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