The decision comes after a 1-0 defeat to Turkey in the World Cup qualifying play-off semi-final on March 26.
The 80-year-old was taken to hospital last week after falling ill during a meeting before a training session, ruling him out of the team’s subsequent friendly in Slovakia on Tuesday.
The departure concludes Lucescu's second stint as Romania coach. During his first spell in charge in the early 1980s, he led the country to the 1984 European Championship, the country’s first appearance at the tournament.
The FRF said Lucescu was expected to take on a new role within the organisation shortly. The search for his successor to lead the next qualifying cycle has already begun.