A spokesperson for the US-backed coalition said the attack followed a Syrian bombing mission against their local allies, the Syrian Democratic Forces (SDF).
But Damascus claimed the plane had been attacking Islamic State positions, adding that the coalition's "flagrant aggression" had caused their pilot to go missing.
"At 6:43pm (16:43 BST), a Syrian regime SU-22 dropped bombs near SDF (Syrian Democratic Forces) fighters south of Tabqa," Operation Inherent Resolve said in a statement.
"In accordance with rules of engagement and in collective self-defence of Coalition partnered forces, was immediately shot down by a US F/A-18E Super Hornet."
An independent monitoring group on social media backed the US version of events, accusing Syrian tiger forces of attacking SDF forces near the Resafa village, south of Tabqa.
The US coalition claimed in its statement it had responded to an attack by Syrian forces on the SDF in the town of Ja'din, near Resafa.
By comparison, the Syrian army said its forces had been fighting IS in a statement released by the government-owned SANA agency.
"The attack stresses coordination between the US and ISIS, and it reveals the evil intentions of the US in administering terrorism and investing it to pass the US-Zionist project in the region," the statement read.
The Syrian Observatory for Human Rights reported that coalition warplanes are currently carrying out "intensive" airstrikes in the area, while "violent clashes" between the SDF and IS continue.
Copyright @ 2019 The New Arab.