An even contest was heading towards a goalless draw until Aleksandar Kolarov's outswinging corner was headed towards goal by Patrik Schick, goalkeeper Emil Audero saved but the ball bounced off De Rossi and into the goal.
Roma, who again left out-of-sorts goalkeeper Robin Olsen on the bench, had to wait nearly two minutes before the VAR system confirmed that De Rossi was onside.
Roma's second win in five games under new coach Claudio Ranieri lifted them to sixth with 51 points from 31 games, one behind fourth-placed AC Milan who lost 1-0 at Juventus earlier on Saturday. The top four qualify for the Champions League.
De Rossi's performance earned glowing praise from Ranieri.
"Daniele is the heart and soul of this team. The captain," he said. "He gets himself and others fired up. He's a leader and I need leaders and people who care about this club. They all follow his example and that's important for me, for Roma and for the club."
Sampdoria were too careless in possession, with moves regularly breaking down in the last third because of wayward passes.
"It's three points that really help us in the league, that really help the mood of the team, that really help the mood of the fans," said De Rossi.
"When there isn't long left in the season you can't try and put your opponents in trouble with passing shapes - you need to put out on the pitch everything you have inside, playing like men and bringing home points."