He entered the National Assembly at the 2009 general election, and in 2010 he was appointed as Deputy Minister of Rural Development and Land Reform in the government of President Jacob Zuma.

Under Zuma's successor, President Cyril Ramaphosa, Nxesi returned briefly to the Ministry of Public Works in 2018 before he was appointed to his current position in 2019.

[5][2] In the aftermath of the election, the ANC announced that it would nominate Nxesi to chair Parliament's Portfolio Committee on International Relations and Cooperation.

He succeeded Gwen Mahlangu-Nkabinde, who was fired amid an investigation into a lease scandal that also implicated police commissioner Bheki Cele.

[10] One of Nxesi's first acts as Minister was to accept, on behalf of the cabinet, a memorandum of protest from the ANC Youth League, which had marched to the Union Buildings to demand land expropriation without compensation.

[17] Shortly after midnight on 30 March 2017, Zuma announced a cabinet reshuffle in which Nxesi was moved to a new office as Minister of Sport and Recreation.

While Sports Minister, Nxesi personally boycotted a tennis match between Israel and South Africa, held in Pretoria during the 2018 Davis Cup.

[27][28] In an open letter, Nxesi wrote:[G]iven the concerns that activists and fellow South Africans are raising regarding the presence of an Israeli team, I believe that it would not be proper for me to attend.

When Ramaphosa announced his new cabinet, Nxesi was returned to his former office as Minister of Public Works, replacing Nathi Nhleko, who was fired.

[33] Pursuant to the 2019 general election, Nxesi was re-elected to his seat in the National Assembly,[4] and Ramaphosa appointed him as Minister of Employment and Labour.

[34] In addition to his permanent ministry, Nxesi served as Acting Minister of Public Service and Administration from April 2022, after the incumbent, Ayanda Dlodlo, left to join the board of the World Bank.

[39] Despite earlier rumours that Nxesi could face a challenge to his SACP leadership,[40] he was re-elected as Deputy National Chairperson in July 2022, now deputising Blade Nzimande.

Their 17-year-old daughter, Lona, died in June 2012 in a car accident near Kroonstad; she was travelling home to Midrand from her boarding school in Bloemfontein.