Following the Iranian revolution of 1979, Najafi returned to Iran and became a faculty member at Isfahan University of Technology in 1979 and he was the chair of the university from 1980 to 1981. He was a faculty member at department of mathematical sciences in Sharif University of Technology from 1984 to 1988, when he moved to government. At the end of the reformist government of Mohammad Khatami and following Mahmoud Ahmadinejad's election Najafi moved back to university and has been faculty in the department of mathematics at Sharif University of Technology working on representation theory. He served as an advisor to Mostafa Chamran. He was the minister of higher education from 1981 to 1984 in the cabinet of then Prime Minister Mir-Hossein Mousavi. In 1989, he became the minister of education under then President Hashemi Rafsanjani and served until 1997. In 1997, he was appointed vice president and head of the Planning and Budget Organization by President Mohammad Khatami, but after a merge of the organization with another he was succeeded by Mohammad Reza Aref in the post. Najafi was an advisor to President Khatami and the senior advisor to the minister of industries from 2001 to 2005. In the 2006 Iranian City and Village Councils elections, Najafi ran for a seat in Tehran City Council. He headed a list named "The Union of reformists". This was the first time Najafi ran in a general election in Iran. He was not seek for a reelection in 2013 election. He was also an advisor to Mahdi Karroubi. He is the cofounder of the Executives of Construction Party. He was nominated as minister of education by Hassan Rouhani. However, the Parliament did not approve his appointment on 15 August 2013. He received 142 votes in favor, 133 votes against, and 9 abstentions. He was appointed head of Cultural Heritage, Handcrafts and Tourism Organization on 17 August. However, Najafi resigned from his position on 30 January 2014 due to health problems, making it the first change in Rouhani's cabinet.
Mayor of Tehran
On 21 July 2017, Najafi was the candidate with the most votes among the seven top candidates for Mayor of Tehran and on 10 August 2017, unanimously elected as the new mayor by the City Council of Tehran defeating Elaheh Koulaei and Mohsen Mehralizadeh. The decision was unofficial, and became effective when the council convened its first official meeting on 23 August. After his office-taking took longer than usual, the council appointed a caretaker on 27 August. Hours later and minutes to midnight the Interior Ministry approved his credentials and he took office. Najafi resigned on 14 March 2018 after a video surfaced of him watching girls dancing, which offended Iranian clerics. However, according to one of the council members, the resignation was due to medical problems.
Arrest
On 28 May 2019, Najafi's second wife Mitra Ostad was found dead in the bathtub of her home in Sa'adat Abad's Armita Tower. Iranian Police announced she was killed by gunshots, with a bullet in her heart and another in her arm. Hours later, Najafi confessed to murder by referral to police. Head of Tehran police's criminal investigation department said he was in detention and discovered the weapons he shot with. A video was also broadcast on these details. On 30 July 2019, he was sentenced to death for murdering his wife. However, he was temporally released from prison on 28 August 2019 after family of his former wife satisfied.
