A BBC Wales investigation has found that supply teachers are paid substantially less when hired through an agency rather than by a school.
NASUWT Cymru called for regulation and for an investigation into agencies' employment practices.
A recruitment body denied exploitation, saying agencies provided skilled teachers, quickly.
The Welsh government said it was up to head teachers as well as the governing body to manage absences.
Speaking to BBC Wales, a supply teacher who did not want to be identified said he and his colleagues were treated unfairly.
"A teacher who has been working for nine or 10 years would get £27,000 or £28,000 a year," he said.
"The most they would be paid through an agency would be £17,500, and that is if you are in continuous employment.
"If you are hired directly by a school you might get £150 or £160 a day, but the maximum you would be paid by an agency is £100 and you could be paid as little as £60.
"There is no regulatory body so there is nothing to say what rate of pay supply teachers get.
"We are the fodder at the bottom of the pile. We only get paid what agencies want to pay us."
Suzanne Nantcurvis, north Wales executive member of the teaching union NASUWT Cymru, said the treatment of supply teachers by agencies was dire, and she believes it could impact on educational achievement.
"I am really shocked by the amount of exploitation and the very poor employment practices of the agencies. One thing necessary is that they are regulated," she said.
"Given that the Welsh government has a standards agenda, it needs to regulate the agencies to make sure qualified teachers are being paid what they should and that classes are being taught by qualified supply teachers when staff teachers are absent."
There are around 5,000 supply teachers in Wales and around 40 agencies that recruit them.
David Pedwell, head teacher of Oakfield Primary School in St Mellons, Cardiff, said schools relied on agencies to book supply teachers.
"Ten years ago we would use a local authority list," he said.
"The emergence of agencies has changed things and they are convenient for schools.
"You need an immediate response when a teacher is sick - the agency is very quick to respond and can provide us with someone within an hour."
If a supply teacher is employed for 12 weeks they are entitled - under Agency Worker Regulations - to the pay of a permanent member of staff doing the same job.
However, agencies are asking supply teachers to sign a contract - known as a Swedish Derogation - to waive this right in exchange for continuous employment or a minimum payment if work is not available.
There are claims that workers have to sign the contract or they will not be offered work.
The supply teacher who spoke to BBC Wales added: "You are pushed into a corner. If you do not sign that contract, you would be out of work a day after the 12 weeks."
Tom Hadley, policy director for the Recruitment and Employment Confederation, the professional body for the UK recruitment industry, denied supply teachers were being exploited.
"The main benefit is that you can get a highly skilled teacher in place in a matter of hours who has all the right checks with all the right skills, so the school is paying for a crucial service," Mr Hadley said.
He said the Swedish Derogation had advantages for supply teachers.
"Even if you're not out on assignment you get paid. It is a trade-off but it is not exploitation. It is legitimate and was included in the regulations after substantial consultation."
The Welsh government said it was the duty of head teachers as well as the governing body to manage absences and that teachers' pay was the responsibility of the UK government.
It added that the school inspection body Estyn was working with the Wales Audit Office on a review which should be completed by the summer.
Supply teachers are being exploited by the agencies that hire them, according to Wales' largest teachers' union.