The 28-year old striker, who had an impressive loan spell with Blackpool in the Premier League last season, has signed a three-year deal at Fratton Park for an undisclosed fee.
The Pride Park exit was always on the cards this summer and now it has happened, Varney is looking forward to the next phase in his career.
"I'm delighted to be here," he told the club's official website.
"Sometimes contracts can drag on through the pre-season, so it was important for me to be sorted early on.
"It's really exciting for me to get to training, meet the boys and push on through the pre-season.
"Once I heard that Portsmouth were interested, it was something that I couldn't turn down.
"It's exciting times at the club. People I've spoken to have told me that it's a club that's going places and it's something I'm really looking forward to."