The three-homer game was the first for a Hurricane since June 2010 (Scott Lawson), while the nine RBI were the most since Chad Rupp had nine in April 1993.
Thompson now leads the nation with 77 RBI and leads the ACC with 18 home runs.
Thompson connected on two-run home runs in the first and fifth innings and added a grand slam in the eighth, bringing his ACC-leading total to a whopping 18 - the most for a Hurricane since Harold Martinez hit 21 in 2010.
"I'm on cloud nine right now," Thompson said after the game. "It was a lot of fun out there. It's fun to come up to bat with guys on base like that, everytime I was up to bat today. I was putting some good swings on the ball."
The grand slam was his third of the season.
"I think I swung at better pitches tonight than yesterday, that's why I was so successful," said Thompson, who went 0-for-3 Thursday. "I was taking strikes that weren't my pitch, and swinging at balls that I could hit well."
Just one night after Thomas Woodrey's complete-game performance guided the Hurricanes to their 10th straight victory, Thompson and the offense stole the show.
Miami outhit the Yellow Jackets 21-4, and the Hurricanes (41-13, 21-8 ACC) captured their ninth home series victory in the last 10 tries.
The victory extended Miami's season-long winning streak to 11 games in front of 2,499 at Mark Light Field.
Miami, who mustered just five hits in a 3-0 series-opening win Thursday, scored four runs in the first and six more in the third, jumping out to an early 11-0 lead and chasing lefthander Ben Parr (5-4) after just one inning.
Not to be overshadowed on Senior Day, lefthander Andrew Suarez (7-1) tossed 6.0 strong innings for the Hurricanes.
"It was a wild one to watch, but it was great," head coach Jim Morris said. "Suarez threw very well, and of course David Thompson was the show tonight with three home runs. We had a lot of guys swing the bat well."