The Israeli army confirmed that it had carried out the strike. A spokeswoman said the car was carrying a militant who had been involved in firing makeshift rockets at Israel.
Witnesses named the dead militants as Emad Assalya and Majdi Hammad. The two dead men and the wounded were from the Popular Resistance Committees, an umbrella group of militants. A local PRC leader was among the wounded, militants said.
The PRC told Aljazeera that it would avenge the death of Assalya and that of all Palestinian militants.
The witnesses said the car was hit by three missiles fired from an airborne drone.
The Israeli military has carried out periodic air raids in the Gaza Strip against militants who fire homemade rockets into the Jewish state.
The strike follows recent days of Palestinian factional violence in the coastal territory. Five Palestinian bystanders were killed in crossfire in incidents on Sunday.