Polls predict a victory over the liberal opposition United Democratic party (UDP), but it remains unclear if Lee's conservative Grand National party (GNP) can secure an outright majority in the single-chamber legislature.
The vote comes amid Lee's waning popularity due to a failure to immediately live up to his "get-the-job-done" image, and because of the resignation of several cabinet ministers on grounds of alleged ethical lapses.
"I'm asking many voters to take part in the polls," Lee was quoted as saying after casting his ballot in Seoul.
"We also promise to do our best in conducting state affairs though it's difficult."
Fearing a record low turnout of the 37.7 million eligible voters, the National Election Commission made an unprecedented move to offer discounted entry fees to museums, parks and cultural facilities.
The new parliament will start meeting on May 30 for a four-year term.
"[South Koreans] are sick and tired of the threat issue [from Pyongyang] … particularly in the election period"
Ok-Ninn Chung, Seon Mun University
Lee won the December presidential election by a landslide with pledges to introduce pro-business measures, boost ties with the United States and get tougher on North Korea.
"The situation is not so favourable but I'll do my best in my job," he said in apparent reference to the global credit crisis.
Lee, a former Seoul mayor and senior Hyundai executive, has been embroiled in a protracted verbal war with North Korea whom he said should first abandon its nuclear programme before getting economic aid.
But Al Jazeera's David Hawkins reporting in Seoul said voters were more worried about the economy than the threats and insults from their northern neighbour.
He said North Korea denied trying to sway the South Korean vote.
Ok-Ninn Chung, a professor at Seon Mun University, told"sick and tired of the threat issue … particularly in the election period" since they have received military threats from Pyongyang for five decades.
Al Jazeera that South Koreans were
Jin Jeong-ahn, 64, a housewife in Seoul, said she voted for a GNP candidate because she believed it would help Lee run state affairs in a more stable manner.
"I like Lee because I think he is an honest man with initiative and drive," she said.
Park Jin, the GNP incumbent in Seoul, is being challenged by Sohn Hak-kyu, the UDP chairman.
"I voted for Sohn as he is the opposition leader," Jung Ho, a 54-year-old barber, said.
"We have to help Sohn maintain his dignity and check the Lee Myung-bak government."
The GNP has called on voters to help the president carry out his economic plans by giving them control of parliament.
Cho Yoon-seon, a GNP spokeswoman, said in a statement on Tuesday that Lee's government was only launched a month ago, and should be given a chance to prove itself.
"It has been just a month since the launch of the Lee Myung-bak government, which the people chose to revive the nation's economy.
"If we turn off the engine even before starting up the economic recovery, the Lee government can't take even one step forward."