Archer follows the exploits of eight dysfunctional secret agents of the International Secret Intelligence Service (ISIS), a fictional New York-based intelligence agency. They are : Sterling Archer, the show's narcissistic, womanizing protagonist, Malory Archer, ISIS director and Sterling's snarky, emotionally distant mother, Lana Kane, Sterling's love interest and mother of his infant daughter, and by far the most professional field agent at ISIS, Ray Gillette, the agency's openly gay bomb specialist, Pam Poovey, the head of the agency's Human Resources department who is often ridiculed by her peers, Cyril Figgis, a mild-mannered accountant-turned-agent, Cheryl Tunt, Malory's delusional, psychotic personal assistant and Dr. Algernop Krieger, a bizarre, morally bankrupt scientist with little regard for the well-being of his subjects.
In yet another attempt to secure funding for ISIS, Malory drags her agents to the luxury winter resort town of Gstaad to protect a Swiss billionaire's daughter from a kidnapping threat. But Archer soon finds out the real threat is his protectee: an underage nymphomaniac who will stop at nothing to bed the world’s greatest spy.
After Malory is wiped out in a Ponzi scheme, she hatches a scheme of her own: selling ISIS - lock, stock and snack machines - to archrival spy agency ODIN. Archer and the rest of the ISIS employees, rightfully fearing for their jobs, must use every trick in the book (ISIS Field Manual, 3rd Edition) to try to stop the sale.
When Archer's favorite call girl suddenly arrives for a visit, Archer is shocked to learn that she claims her new baby boy was fathered by him. She obtains a court order that forces him to take a paternity test in hopes of proving her claim.
Archer and Lana head to Louisiana to stop an ecoterrorist from blowing up a natural-gas pipeline. (Archer’s also looking forward to a Big Easy vacation.) Back at ISIS headquarters, Mallory orders the staff to go green to get “freebie socialist tax credits.” A flashback recalls Lana’s introduction to ISIS.
When members of Woodhouse's famed WWI Royal Flying Corps squadron start dying mysteriously, Archer tries to track down the killer.
Cyril agrees to help George Spelvin inject a virus into the ISIS mainframe so Cyril can defeat the virus and be seen as a hero.
On Malory's orders, Lana helps Hollywood star Rona Thorne (voice of Rachael Harris) research her role in a spy thriller while Malory writes a role for herself in the movie (with Cyril's reluctant assistance). Meanwhile, Pam steals Rona's diary.
Breast cancer strikes the Archer family---Sterling has it. "I'm trying to stay positive," he says. "I can beat this." But before surgery, he wants to bond with young Seamus (even though he isn't actually the baby's father) and take a Las Vegas vacation.
When Archer discovers that the chemotherapy drugs he has been taking are phony, he goes on a rampage against the Irish gangsters behind the scheme. He also makes friends with a fellow marijuana-toking cancer patient (voice of Joan Van Ark). Meanwhile, Cyril learns why Krieger is fluent in Portuguese.
Pam is abducted by kidnappers who mistake her for Cheryl. It seems that Cheryl wasn’t completely forthcoming about her background when she applied for her job at ISIS.
When a mysterious stranger summons Malory and her intrepid ISIS agents to Monaco, all bets are off! Well, actually all bets are on. Because Monaco is basically one giant casino, and Archer has $4 million in untraceable bearer bonds. Also, it's Gran Prix week, so you can just forget getting a hotel room
Archer's search for his father's identity leads him into hot water. Agent Barry Dylan is sent to rescue Archer.