The air strike killed at least eight civilians in the Yarmuk camp, which has been rocked by intermittent violence over the past few months, the Britain-based watchdog said, addding that others were in critical condition.
The raid came hours after the rebel Free Syrian Army (FSA) made significant advances in Yarmuk, a camp resident told AFP by Internet.
"There is a state of real war in the camp now," Abu Mohammed said. "There are intense battles between the Free Syrian Army and the Popular Front for the Liberation of Palestine-General Command," a hardline Palestine militant group that has long been a Damascus ally.
"The air strike happened because of the FSA's advances in the camp," he said. "The two are obviously linked."
PFLP-GC fighters were locked in fierce clashes with rebel units, some of them Palestinian, the Observatory said.
The PFLP-GC, headed by Ahmed Jibril, has sided with the regime of President Bashar al-Assad throughout the revolt, while some Palestinians have fought alongside the rebels.
Residents told AFP that one missile hit the Abdel Qader Husseini Mosque in the heart of the camp, which was acting as a makeshift shelter for some 600 people who had fled homes in nearby districts.
Abu Mohammed said a second missile struck near a school housing hundreds more displaced people.
"Although the people taking shelter in the Fallujah School are afraid, they really have nowhere else to go," he said.
Amateur video posted online by activists showed broken glass strewn on the ground by the mosque, and several bloodied bodies laid out at the entrance.
The Observatory earlier reported that a toddler was killed in shelling of Yarmuk by the army. Activists in the camp said Yara Abu Shaira was not yet two years old.
The air strike on Yarmuk was the sixth on Sunday on flashpoint districts of south Damascus, the watchdog said.
Warplanes also bombarded the nearby districts of Al-Hajar al-Aswad and Assali, scene of intense fighting between troops and rebels, it added.
"The army feels it has to step up its campaign to suppress the insurgency in south Damascus, and that it cannot fight off rebels without resorting to air power," said Observatory director Rami Abdel Rahman.
"As for the Palestinians, they are divided over the conflict, and are fighting on both sides," he added.