The program, designed to make voting easier for disabled residents, is part of a five-county pilot in the north-western state.
The counties are voting to nominate candidates to replace David Wu, who resigned from the US House of Representatives amid a sex scandal.
Voters in Oregon have cast their ballots entirely by post since 2000.
As voting gets under way on Tuesday, election workers will canvass the five Oregon counties bearing iPads and portable printers, stopping at parks, community centres and nursing homes.
Residents do not officially "vote" on the tablet, but instead use software developed by Oregon's elections division to cast their ballot, which is then printed out to be mailed back to the state.
The pilot program is intended to replace older tools designed for accessible voting in Oregon, often laptops with modifications that were stored in two suitcases.
Voters with poor vision can adjust the font size and screen colours, or have the candidate names read off.
One of the first users of the iPad ballot was 75-year-old Lewis Crews, who has severe arthritis and avoided using a pen to mark his ballot.
"It's a lot simpler for me. I think it's a great setup they got," Mr Crews told the Associated Press news agency.
If the pilot programme is successful, state elections officials say they will make the technology available across Oregon.
Apple donated five iPads for the scheme, and the state spent about $75,000 (Â£46,700) to develop the necessary software.
Oregon would need at least 72 iPads to make it a state-wide program, according to Steve Trout, state elections director.
That would bring the total cost for the computers to about $36,000, with a smaller total for the portable printers.
In its last two budgets, Oregon spent more than $325,000 on accessible voting tools.
Residents in parts of the US state of Oregon are to cast their votes by iPad during a special election on Tuesday.