One person was reportedly killed and several injured as police dispersed the protesters - supporters of the Muttahida Qaumi Movement (MQM) party.
They were reportedly angry over a lack of coverage of a hunger strike.
Local media said the attack came after MQM's London-based leader Altaf Hussain called the protest. MQM wields significant power in Karachi.
It has has faced accusations of racketeering, abduction, torture and murder. The party denies links to crime.
"MQM workers fired shots at the ARY office, ransacked the premises and set fire to a police mobile," a police official told news agency Reuters.
Kashif Abbasi, a senior anchor for ARY, told Pakistan's Dawn newspaper: "They are Muttahida people. He [Mr Hussein] ordered them to do it and within 10 minutes all this happened."
Earlier on Monday, the MQM protesters had gathered outside a local press club where some had been on hunger strike to protest against alleged attacks on the group by security forces.
Wasay Jalil, a London-based spokesman for MQM, said that the MQM supporters were protesting peacefully and police fired first.
He told the BBC: "They were there to protest peacefully against the media trial of MQM... The MQM supporters did not commit any violence."
Mr Jalil said that one member of MQM staff was shot dead in clashes with security forces and a supporter was shot in the neck and wounded, although this could not be independently confirmed.
Dr Seemin Jamali, Head of Emergency at a nearby hospital, told Dawn: "At least one person was brought dead [to the hospital] while several others were injured."
Protesters in Karachi have fired shots at the offices of local TV station ARY and attacked staff, police said.