It was not immediately clear who committed the crime. Before sunrise, a group of armed men pulled up in three vans at the La Playa Men's Club in the city of Salamanca, burst into the premises and opened fire, local media reported.
A video taken after the shooting from the street near the nightclub showed a line of police vehicles. A woman wailed uncontrollably in the background as an ambulance drove into the area.
According to a statement from the Guanajuato state prosecutor's office, 13 men were found dead in the nightclub, and another two died after being taken to hospital. It added that its agents were investigating the crime.
More than a decade after the launch of a militarized effort against drug cartels that has led to some of Mexico's bloodiest years on record, the latest effort will test the new government's ability to curtail the reach of organized crime.
Lopez Obrador took office on Dec 1, vowing to fight crime in a new way.