Patrolling officers spotted a white car arrive outside Bar Bambi in Flinders Lane in Melbourne's CBD about 4.45am on Friday.
The pair, both 16, allegedly ran from the car holding a red jerry can before smashing a window of the licensed venue and attempting to pour fuel inside.
Observing officers intervened and arrested the two boys as the driver fled in the car, which has not been located.
The arrested teens, who are from the Casey and Monash areas in Melbourne's southeast, are being interviewed, as detectives work to identify possible links to previous incidents.
A single red jerry can sat outside the empty venue located in the CBD's ACDC Lane, which remained taped off by police.
The popular nightlife venue has been targeted by alleged arsonists twice before, including on April 25 when three teens were charged over an alleged attack.
Victoria Police have increased patrols around Melbourne's entertainment precincts following the spate of attacks on licensed premises.
Operation Eclipse officers investigating the incidents believe organised crime syndicates are involved and have been tasked with finding organisers and those pulling the strings.
Separately, police arrested two teens over the alleged firebombing of The George Hotel in South Melbourne after five Molotov cocktails were thrown towards the venue on May 2.
No one was inside at the time and the fire was put out quickly by responding authorities, leaving minimal damage.
Detectives raided two homes on Friday morning where they seized a gun, several electronic devices and a quantity of drugs.
They arrested and are interviewing two 17-year-old boys.
Officers have also arrested and charged a Tarneit man over an investigation into extortion demands on two other venues in Melbourne's CBD.
The 20-year-old allegedly made two demands for money to venues on Flinders Lane and Lonsdale Street over social media on May 7.
Detectives seized several knives, ammunition, and a phone from his home before charging him with possessing a prohibited weapon without exemption and possessing cartridge ammunition without exemption.
He was bailed to appear at Wyndham Magistrates Court on June 12.
The arrests come as police investigate a separate suspicious truck fire in Sunshine North in Melbourne's west on Thursday evening.
Two men allegedly smashed the windows of a parked truck before pouring an accelerant inside and igniting it.
The pair unsuccessfully tried to set another truck parked next to the vehicle before fleeing the scene in a white car.
No one was inside the trucks at the time, and no arrests have been made.
