Cesc Fabragas' Como came back from Davide Zappacosta's 18th-minute volley to claim all the points in the Italian top flight for the first time since beating Torino on the final day of the 2002/03 season.
Como levelled through Gabriel Strefezza's fine effort right after half-time and were ahead in the 54th minute when the unfortunate Sead Kolasinac deflected Nico Paz's strike into his own goal.
Alieu Fadera completed a historic victory for Como against fellow Lombardy club Atalanta with a brilliant individual strike which stunned the home fans.
Como, owned by tobacco giant Djarum, lept out of the relegation zone and up to 15th place on five points following Tuesday's win, a point behind Europa League holders Atalanta who sit 12th after a strange start to the season.
Gian Piero Gasperini's Atalanta have lost three of their opening five Serie A fixtures and were unlucky to only draw 0-0 with Arsenal in the Champions League on Thursday.
Ademola Lookman pulled one back from the penalty spot in the ninth minute of stoppage time, too late for the hosts to mount a comeback.
