Candidates of the ruling Congress-led UDF, CPI(M)-led LDF and BJP are engaged in three-cornered fight in the rural constituency, located about 15 km south-east of the capital.
According to official sources, impressive voter turnout was reported from most parts of the rural segment in the initial hours itself.
A total of 1.6 lakh voters are eligible to cast their ballots in the polls.
Though the main battle in Neyyatinkara is between R Selvaraj (Congress) and F Lawrence (CPI-M) of LDF, entry of former Union Minister and senior BJP leader O Rajagopal has virtually turned the contest into a three-cornered one.
The by-poll is especially crucial for CPI-M as it is their sitting seat, vacated by R Selvaraj, who has joined Congress and is now contesting on the 'hand' symbol.
The poll also came at a time when CPI-M is on the defensive with several of its activists being arrested in connection with the murder of RMP leader T P Chandrasekharan at Onchiyam in Kozhikode on May 4.