Gabriel Logan and Lian Xing are operatives of The Agency, on the trail of Erich Rhoemer, an international terrorist. In August of 1999, Agent Ellis attempted to infiltrate Rhoemers narcotics operation in Guacimo, Costa Rica, but was discovered and executed by ex-KGB agent Mara Aramov. Rhoemer then ordered Anton Girdeux, a French mercenary, to burn down the plantation to hide the evidence of their Syphon Filter research.
In Washington, D.C., Edward Benton, the Agency Deputy Director, is briefing Logans mission to Agency Director Thomas Markinson and a shadowy, unnamed figure. Several weeks later, Gabe and Lian investigate a mysterious viral outbreak in the Himalayas, which leaves only a single survivor (A fact that Lian describes as impossible).
The game begins one month after the events in Costa Rica. Rhoemer and his terrorists have launched an assault on Washington, D.C. Gabe defeats Pavel Kravitch, Rhoemer's communications expert, which allows him to gain entry to the Washington Metro. Once inside, an explosive goes off leaving Gabe trapped underground. He pursues Aramov, catching her in the tunnels before heading to a nearby park to aid in the defusing of several viral bombs, where he learns that Aramov has escaped custody. Making his way to the Freedom Memorial, Gabe takes on and defeats Jorge Marcos, Rhoemers trigger man, and Girdeaux.