Buffalo traded the No. 9 pick plus their first and fourth-round picks in 2015 to move up and select the six-foot-one Watkins at No. 4.
"(Jadeveon) Clowney was just slightly behind him," general manager Doug Whaley said. "When he was gone No. 1, it was a no-brainer. It would've been a decision (if Clowney was there). But the way we ranked them, it was Sammy first."
Watkins, 21, hauled in 101 passes for 1,464 yards and 12 touchdowns as a junior at Clemson, earning first-team All-ACC and second-team All-American honors.
On Sunday, the Bills, who went 6-10 and finished in last place in the AFC East in 2013, became the first team to open preseason training camp.
- Chris Johnson