Sunday's ballot is the first round in the election and if neither presidential candidate garners a majority, the elections will go to a second round with the two top candidates standing in a runoff on June 20.
Lucia Newman, Al Jazeera's correspondent in Bogota, said: "The is an extraordinarily competitive race. One of the most competitive the country has seen in many, many decades."
According to Al Jazeera's Teresa Bo, in Ciudad Bolivar in Bogota, the polls are expected to be busy.
"Many experts are saying that this election is going to have the highest turnout in Colombia's history," Bo said.
"Generally in Colombia about 40 per cent of the population vote. But experts are saying this time around about 50 per cent of the population will cast their ballot."
Bo said that a proportion of voters, typically supporting Santos, were focused on security and another group, generally backing Mockus, is prioritising healthcare and unemployment as election issues.
The vote also comes amid warnings from the Revolutionary Armed Forces of Colombia (Farc) rebel group that it will try to disrupt the polls.
In response to the threats security has been stepped up across the country, with thousands of soldiers and police on heightened alert in anticipation of possible attacks by the left-wing guerrillas.
Santos on Saturday spoke about how his party have regained control of the country during their political term and have returned Colombia to "peace and tranquillity".
Santos was a key figure in freeing former presidential candidate Ingrid Betancourt and three US contractors held hostage by the Farc in 2008.
He has relied on Colombia's advances against the rebels under his leadership, arguing he is the best candidate to carry on with Uribe's security policy.
'No to fear'
Former mayor of Bogota and head of Green Party.
Pledges to continue Uribe's security policies but also promises to bring in governmental transparency.
Electoral campaign emphasised economic reforms and tackling high unemployment.
Juan Manuel Santos
Defence minister under Uribe.
Closely involved in the battle against Farc rebels.
His strategies against fighting the Farc have been marred by allegations of human rights abuses.
Also vows to continue Uribe's security policies.
Santos also has portrayed himself as the best candidate to deal with neighbouring Venezuela and Ecuador, both countries with contentious relations with Colombia.
Santos' campaign rallies have been punctuated by slogans saying "No to fear" in reference to the 46-year-old Farc, the oldest insurgency in the Americas responsible for murders, kidnappings and extortion, and generalised crime.
"The Farc intend to interfere in the elections. In some areas of the country they are threatening people to stop them from voting for me," Santos told supporters on Saturday.
Under Uribe's tenure, military spending increased from three per cent of gross domestic product to 4.1 per cent, boosting the security forces from 220,000 men to 425,000.
Anti-Farc operations over the same period thinned the rebels' ranks from an estimated 17,000 in 2002 to around 7,500.
Mockus, for his part, has also promised to crack down on the rebels though he has also emphasised the economic policies he hopes to implement.
Colombia currently has the highest unemployment rate in South America and Mockus has pledged to create more jobs.
His base of support is the relatively better-off citizenry of the capital, while Santos has aimed his efforts at Colombia's large population of rural and poorer voters.