Polling to choose the 13th president started simultaneously at the national and state capitals.
MPs were seen queuing up in Parliament House outside the polling booth in Room No 63 as voting began at 10 a.m.
Voting was brisk with Bapi Raju Kanumuri, the Congress MP from Narsapuram in Andhra Pradesh, being the first MP to vote.
"My blessings are with Pranab Da. I was the first to vote," Kanumuri told IANS as he came out from the polling station.
DMK's M.K. Alagiri, Biju Janata Dal (BJD) member Bhartruhari Mahtab and Congress' Pratap Singh Bajwa were among the early voters.
As voting picked up, many MPs, including women members, were seen in the queue waiting to cast their votes.
Mukherjee, who has a clear edge over opposition-favoured Sangma, came to vote shortly after 11 a.m. Congress MPs were seen greeting him.
Prime Minister Manmohan Singh and Congress president Sonia Gandhi accompanied Mukherjee as the leaders cast their ballot one after the other amid camera flashlights.
Congress general secretary Rahul Gandhi also voted shortly after.
The leaders didn't speak to the media but waved towards a battery of reporters covering the event.
Bahujan Samaj Party (BSP) Mayawati and Samajwadi Party MP Jaya Bachhan were among the women voters.
From the opposition camp, Bharatiya Janata Party (BJP) leaders Prakash Javadekar and Rajnath Singh were among the early voters.
Voting was also under way in all states for assembly members who along with Lok Sabha and the Rajya Sabha MPs together make up India's electoral college.
The college has 4,120 assembly members and 776 members of parliament.
Polling will continue till 5 p.m.
The votes will be counted Sunday, three days before President Pratibha Patil five-year tenure ends.