Four Syrians, one Iranian national and three other non-Syrian fighters were among the casualties of the strike carried out on Saturday, the war monitor said.
"A convoy of Iranian forces and allied militia was hit by air strikes as it drove near Al-Tanf base," the head of the monitoring group Rami Abdel Rahman said.
"We do not know if it is planes of the international coalition", led by Washington to fight against the Islamic State group (ISIS), he said.
He said he could not confirm the strike had been conducted by the US-led coalition present in the region.
The coalition did not immediately reply to an AFP query.
The report came days after Iran was said to have given ballistic missiles capable of striking Tel Aviv to Shi'ite proxies in Iraq.
Iran was also reported to have been developing the capacity to build more there to deter attacks on its interests in the Middle East, according to Iranian, Iraqi and Western sources.
The Zelzal, Fateh-110 and Zolfaqar missiles in question have ranges of about 200 km to 700 km, putting Saudi Arabia's capital Riyadh or Tel Aviv within striking distance if the weapons were deployed in southern or western Iraq.
Several strikes against the Syrian government or allied forces have been in the past attributed to US forces deployed as part of a multinational coalition against the ISIS group.
The base, set up in 2016 near the borders with Iraq and jordan, was also used for the training of so-called "vetted opposition" to the regime of President Bashar Assad.
Despite a 55-kilometre (34-mile) deconfliction zone around the base, Al-Tanf is seen as a potential flashpoint between US and Iranian or Tehran-backed forces.
The presence of a US base in the arid border region has been a source of tension and its dismantling is often cited as a key demand by Damascus and its allies.
Beyond the battle against IS jihadists in their nearby desert hideouts, analysts say Washington sees the base as disrupting Iranian efforts to open a east-west land corridor from Tehran to Lebanon.
Syrian state media said on Sunday that loud blasts coming from the Mezzeh airbase early the same morning were from an explosion at an ammunitions dump caused by an electrical problem.
Syrian military officials later said that the explosions, which were originally attributed to Israel, were in fact caused by the electrical malfunction.
Reuters contributed to this report.