After more than five years in opposition, he built a coalition of 12 parties in the wake of the 2012 Lesotho parliamentary election and was appointed prime minister.

In 2020, Thabane faced pressure to resign as prime minister due to his alleged involvement in his ex-spouse's murder.

[14] 18 MPs crossed the floor to join the ABC in opposition on 13 October 2006;[11][15] 17 of these (including Thabane) had been LCD members, and one had been an independent.

[16] The ruling party was left with 61 of the 120 parliamentary seats; with such a precarious majority, Mosisili requested the dissolution of Parliament, and an early election was called for February 2007.

[21] The LCD's reluctance to engage in talks regarding the political situation prompted Thabane on 18 October 2007 to threaten street protests to pressure the government into holding a new election "if they continue to fail to cooperate".

[23] After a 22 April 2009 assault on Mosisili's residence, which was believed to have been a failed attempt to kill him, police said that retired officer Makotoko Lerotholi, a bodyguard of Thabane, was suspected of involvement in the attack.

[24] After more than five years in opposition, Thabane formed a coalition with other parties in the wake of the 2012 Lesotho parliamentary election and was appointed prime minister.

[5][13] Thabane fled to South Africa on 30 August 2014, alleging that the military was attempting to take power and wanted to kill him.

[26] Thabane's party failed to attain a majority in the 2015 snap election and was unsuccessful in forming a coalition government.

[27] Following the opposition's June 2015 boycott of parliament to protest the government's alleged disinterest in investigating circumstances surrounding Brigadier-General Maaparankoe Mahao's death, Thabane and two other opposition party leaders left for South Africa and did not attend any parliamentary sittings, citing security issues and instability in the country.

On 12 February 2017, they returned to Lesotho, declaring that Mosisili no longer commanded a parliamentary majority and vowing to oust him in a vote of no confidence.

[31] In October 2017 rumours that Thabane had been hospitalised in South Africa were dismissed by a spokesperson as propaganda intended to destabilise Lesotho.

He announced his intention to relinquish the party leadership in January 2022, citing poor health and his advanced age.

[41] In the first week of January 2020, the ruling All Basotho Convention (ABC) party asked him to resign over his suspension of the police commissioner Holomo Molibeli, who had linked him to Lipolelo's murder.

[44] On 21 February 2020, Thabane failed to appear in court for the case, with his son saying he had traveled to South Africa to see a doctor.