Ortega, a 71-year-old former Sandinista guerrilla fighter, took the oath in Managua with the presidents of Venezuela, Bolivia and Taiwan in attendance. He let his wife speak first.
"I want to say to Nicaraguan women, here we are, we are going forward together and we have the future ahead of us winning the spaces that we deserve," Murillo said.
Ortega and Murillo were elected in November with 72.5 per cent of the vote, but with a high rate of abstentions. Their party won 71 of the 92 seats in parliament.
Nicaragua could face economic challenges in Ortega's third 5-year term amid a steep drop in aid from Venezuela, which has funded many social programs. A law is also being considered in the US that could block Nicaragua's access to loans from international lending organizations, pushed by American legislators critical of a lack of government transparency.
Violeta Granera, head of the opposition Broad Front for Democracy, said critics of Ortega will continue to be in the streets demanding that the country return to its institutions and rule of law.
"Nothing changes here," she said. "The abstention in November was a clear message that the population calls for free, transparent, competitive and observed elections.