Clemson quarterback Deshaun Watson did not return after a first-quarter knee injury. Cole Stoudt threw three interceptions after replacing Watson, including one Chris Milton returned 62 yards for a touchdown.
With the loss by Clemson (7-3, 6-2 Atlantic Coast Conference), No. 2 Florida State clinched the ACC's Atlantic Division before playing Miami on Saturday night.
Justin Thomas' 65-yard run set up his 5-yard touchdown pass to DeAndre Smelter in the third quarter as Georgia Tech (9-2, 6-2) earned its fourth straight win and kept its hopes alive in the ACC's Coastal Division.
Georgia Tech fans rushed to the field after the win.
Thomas completed 8 of 11 passes for 102 yards with a touchdown.
Clemson couldn't overcome the loss of Watson and was held to 190 yards.
Clemson led 3-0 and was driving inside the Georgia Tech 10 when Watson's injury changed the game.
Watson, who returned as a starter after missing three games with a broken bone in his right hand, hurt his left knee when making a cut on a 7-yard run for a first down. He fell to the ground and grabbed his knee before being escorted to the sideline and then to the locker room.
Clemson said at halftime Watson would not return to the game. No details of the injury were immediately provided.
On his third play after Watson's injury, Stoudt threw his first of three interceptions. Stoudt rolled to his right before turning and throwing to his left, but Golden had an open field after stepping up for the interception to give Georgia Tech the lead.
Stoudt's first pass of the second half was intercepted by cornerback D.J. White, setting up a field goal for the Yellow Jackets.
Milton's interception return pushed Georgia Tech's lead to 25-6 late in the third quarter. Clemson turned to its third quarterback, sophomore Nick Schuessler, on its next possession.
Stoudt completed only 3 of 11 passes for 19 yards with three interceptions. Watson completed 5 of 7 passes for 27 yards and ran for 40 yards before his injury.
Clemson tried to focus on its running game. Wayne Gallman ran for 82 yards on 14 carries, but the Tigers were held without a touchdown. Ammon Lakip kicked field goals of 27 and 32 yards.
Georgia Tech running back Broderick Snoddy's 46-yard run, the longest of his career, set up a 25-yard field goal by Harrison Butker in the second quarter. Later in the quarter, Snoddy had to be carted off the field after suffering an apparent right leg injury.
With Snoddy on the cart and still on the field, Georgia Tech's team circled the junior in a big huddle before he was wheeled off the field.
Georgia Tech center Freddie Burden limped off the field with an apparent leg injury later in the second quarter and did not return.
Watson injured, Clemson loses in Atlanta
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