But Mockus was not conceding defeat, despite garnering less than half the votes his opponent did.
"More than three million citizens have united in what has become a wave of green hope. We know that together we can transform society, we know violence, inequality and corruption are not our destiny - they are problems we can overcome," he told his supporters.
Opinion polls had shown Santos in a tight race with Mockus, well ahead of the seven other candidates.
Speaking from Bogota, Lucia Newman, Al Jazeera's Latin America editor, said the "extraordinarily competitive" race had been expected to be one of the closest the country had seen in many decades, but Santos had emerged with a one-sided win instead.
Jorge Restrepo, a political analyst, told Al Jazeera that the discrepancy between the opinion polls and the election results may have been due to pre-election surveys giving the urban opinion more weight.
"Colombia still has a significant proportion of the rural population who mostly support the security and continuation of Uribe's security policy," he said.
"We may have also underestimated the very many strengths and the importance of Uribe's opinion."
Al Jazeera's Gabriel Elizondo, reporting from Colombia's second largest city, Medellin, said even the Santos camp was surprised by the margin of its candidate's win, describing the results as exceeding all expectations.
Our correspondent said either Santos connected with voters on health and social issues or on his security policy.
"People here are not voting for change in this election but for an extension of Uribe's security policy," he said.
In response to warnings from the Revolutionary Armed Forces of Colombia (Farc) rebel group that it would try to disrupt the polls, security was stepped up across the country.
Santos was a crucial figure in the operation that freed Ingrid Betancourt, a former presidential candidate, and three US security contractors held hostage by the Farc in 2008.
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.
He has relied on Colombia's gains over the leftist rebels under his leadership, arguing he is the best candidate to carry on with Uribe's tough security policy.
Santos also has portrayed himself as the best candidate to deal with neighbouring Venezuela and Ecuador, which have tense ties with Colombia.
Santos' campaign rallies have been punctuated by slogans saying "No to fear" in reference to the 46-year-old campaign by Farc, blamed for murders, kidnappings, extortion, and general crime as the oldest insurgency in the Americas.
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, also promised to crack down on the rebels though he also emphasised the economic policies he hoped to implement in a country that has the highest unemployment rate in South America.
Al Jazeera's Teresa Bo, reporting from Bogota, said Mockus' supporters had gone from shock to anger to disappointment at Sunday's result.
Although his supporters alleged fraud, Mockus himself said the election had been clean.
And lagging far behind his rival, Mockus had now started talking about forming alliances, our correspondent said.