The Costa Rican club shocked Frank de Boer's side 3-1 in Costa Rica on Thursday, giving Herediano a massive advantage heading into the second leg.
Atlanta's poor night started early with Leandro Gonzalez Pirez handing Herediano the opening goal. The veteran defender headed a backpass towards Brad Guzan, but left it short as Jose Guillermo Ortiz pounced to give the hosts a seventh-minute lead.
That lead doubled in the 34th minute as Herediano fired again via Randall Azofeifa with Ortiz providing assists.
But Atlanta responded just seven minutes later as offseason signing Gonzalo 'Pity' Martinez assisted Julian Gressell to give Atlanta life and a vital away goal.
In the second half, though, Gresell was caught sleeping on a set piece, allowing Esteban Granados to turn home an Azofeifa cross to seal the home win.
Atlanta will now return to a temporary home of Fifth Third Bank Stadium for the second leg as they will host at the 10,500-seat stadium instead of their home of Mercedes-Benz Stadium.
Sporting Kansas City ran away with a home victory over Toluca, topping the Mexican side 3-0 at Children's Mercy Park in the night's first match.
Having coasting through most of the first half, Sporting KC took the lead in the 35th minute against the 15th-place Liga MX side.
After wasting an earlier chance, Krisztian Nemeth atoned for his mistake by patiently finishing to give Sporting KC the lead just before halftime.
Seven minutes into the second half, Gerso Fernandes scores to make it 2-0, rocketing a shot into the roof of the net.
Ilie Sanchez made it three with the best goal of the night as the midfielder unleashed a long-distance volley into the back of the net to lock up Sporting KC's win heading into the second leg.
Sporting KC will visit Mexico next Thursday knowing that an away goal would all but seal a spot in the competition's quarterfinal round.