Shoigu, the highest ranking Russian official to travel to Syria since the conflict erupted five years ago, was sent by President Vladimir Putin for the surprise meeting with Moscow's long-time ally Assad, the Syrian state news agency SANA said.
"The talks focused on military cooperation between the two countries and joint action to fight against terrorist organisations on Syrian soil," it said.
In Moscow, the defence ministry said the discussions centred on "current questions of military and technical cooperation... As well as certain aspects of the cooperation in the fight against terrorist groups operating in Syria".
US military officials "expressed strong concerns about the attack on the coalition-supported counter-ISIL (Islamic State) forces at the Al-Tanaf garrison, which included forces that are participants in the cessation of hostilities in Syria", Pentagon spokesman Peter Cook said.
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The Pentagon "emphasized that those concerns would be addressed through ongoing diplomatic discussions on the cessation of hostilities", he said.
US defence officials have said Russian warplanes carried out raids in Al-Tanaf targeting a meeting of combatants supported by the US-led coalition that was held to coordinate the fight against IS jihadists in Syria and Iraq.
Russia, however, said it had not carried out any strikes targeting opposition forces included in a ceasefire brokered by Washington and Moscow that excludes IS, without mentioning Al-Tanaf.
Shoigu, whose country's military intervention since last September turned the tide of the conflict in favour of Assad's regime, also inspected Russia's air base in Hmeimim in the Syrian coastal province of Latakia, his ministry said.
The West has repeatedly accused Russian forces of also targeting non-jihadist rebels with air strikes in an effort to prop up the regime.