Francesco Totti struck twice, once from the spot, while Samp's Sergio Volpe also saw red in the controversial clash.
Totti opened the scoring with an audacious chipped spot-kick awarded for Stefano Lucchini's shirt tug on Matteo Ferrari.
"Lucchini told me that he had his shirt pulled first. I want to see how many of these fouls get punished over the course of a year. The penalty is debatable," slammed Mazzarri.
"Considering the way the game went, we did not deserve to lose, as we had more chances than Roma and Alexander Doni was Man of the Match.
"At the end of the day, incidents decide a game. If I think of the penalty, the fouls awarded to the home side in midfield and Volpi's dismissal, then it all adds up. With the second booking incident, our captain was trying to get out of the way."
Roma boss Luciano Spalletti dismissed Mazzarri's claims.
"My team played a tough game and this is what you need at a time like this, when you're not as sharp as you'd like to be," said Spalletti.
"We deserved to win, so I compliment my players. We allowed Samp a few chances and Doni did brilliantly to deny them, but for the rest of the match we did well. We don't have a very physical side, so I introduced Marco Cassetti to give us more substance pushing forward.
"We are going well, but have to do more if we are to catch Inter. I don't like to see quality football that ends up being futile, as that can lead to stupid mistakes."