Mogherini came to Geneva, where peace talks are under way, following a request from United Nations peace talks mediator Staffan de Mistura, making an EU call to both sides that the flagging negotiations move forward.
"It is important not only for the Syrians, but for the Europeans that this process starts, works and delivers," Mogherini told journalists.
She added that Tuesday's bombings in Brussels, claimed by the Islamic State group, had put renewed focus on global efforts to combat the jihadists.
"If we want to tackle this threat, we need… to accelerate and consolidate our common work to put an end to the war in Syria, and concentrate our forces on (IS)," she said.
The regime's lead negotiator Bashar al-Jaafari described his talks with Mogherini as "the first direct meeting with (a) high representative of the European Union... since the crisis began."
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The EU official stressed that the Jaafari meeting did not imply a change in Europe's stance towards President Bashar al-Assad's government.
Asked if the EU still insisted on Assad's departure as part of any peace deal, Mogherini said, "the European Union sticks to the common position it has... on the need for a political transition in Damascus.
"I think I'm clear enough," she added. "There is no change in policy."
Mogherini also met with the main opposition High Negotiations Committee (HNC), which is supported by the EU.
The HNC has demanded that Assad leave power before any transitional government can formed.
Damascus has ruled out any discussion of Assad's fate and described his departure as a "red line" for the talks.
De Mistura is due to hold another day of talks on Thursday before a scheduled pause, with negotiations due to resume next month.