A 40-seat "Bio-Bus", which runs on biomethane gas generated from sewage and food waste, has been running a full service since March.
Operator First West of England now wants to run 110 gas-powered double-decker buses in Bristol.
It has submitted a proposal to the government to run the expanded service.
First West of England's Jenny MacLeod said: "If we are successful we will be leading the way in creating a fully sustainable public transport network that can really make a difference to people in and around Bristol."
Rival operator Wessex Bus and partners GENeco have also applied for a government grant to run 20 bio-buses in the city by 2019.
The two companies have submitted a joint bid to the OLEV (The Office for Low Emission Vehicles) Low Emission Bus Scheme for a grant of Â£2.5 million to support the project.
The biomethane gas for the buses is generated at Bristol sewage treatment works in Avonmouth run by GENeco, and the company hopes to build a permanent refuelling station at the site.
Antony Goozee of Wessex Bus said: "This is a great opportunity to increase the number of gas-powered buses on the streets of Bristol and surrounding area, which will significantly improve air quality.
"We believe this would be the most sustainably fuelled fleet in the UK, as it will be the only fleet where the buses are actually powered by treatment of sewage and inedible food waste from the local community."
Fleets of buses powered entirely by human and food waste could be rolled out in Bristol after the success of a pilot service.