The 25-year-old, who can also operate in midfield, fell out of favour under Stoke boss Mark Hughes and was loaned out to Wigan Athletic last season.
Shotton was linked with a number of Championship clubs, but it is Steve McClaren's promotion-hopefuls who have won the race for his signature initially on loan before he is reportedly set to sign a three-year contract.
Having graduated from Stoke's academy, Shotton went on to play in the Premier League and the UEFA Europa League but became increasingly frustrated with a lack of first-team football.
"It's a move has been on the cards for a few weeks," he told Derby's official website.
"We've spoken, discussed a few things and I'm here now and ready to go.
"I am itching to be playing first-team football again; that's what it is all about.
"I've missed playing regularly and after going on loan to Wigan Athletic last season I was on the bench a few times for Stoke, without getting on the pitch.
"Steve McClaren believes in me and I am looking forward to joining this team and pushing forward."
Shotton could make his debut in Tuesday's League Cup second-round tie at home to Charlton Athletic.
