After coming into conflict with Wade, he was removed from his post as President of the National Assembly in November 2008; he consequently founded his own party named the Alliance for the Republic (APR) and joined the opposition.

Under Sall's leadership, significant infrastructure projects, including a new airport and town near Dakar, highways, express trains, a national stadium, and a road link to Mali, were completed.

Internationally, he earned praise for his diplomatic efforts, advocating for African debt cancellation, bolstering anti-terrorism measures, and condemning military coups.

He contributed to resolving conflicts in the country's Casamance region and played a crucial role in ousting dictator Yahya Jammeh in neighboring Gambia in 2017.

[4] At home, Sall stirred controversy for undemocratic maneuvers, including repressing the political opposition in Senegal and attempting a self-coup, which sparked the 2023–2024 Senegalese protests.

He soon left And-Jëf, since he did not agree with the ideas of the movement or Savané's use of a boycott strategy against the PS in the 1983 election, in which Sall voted for the liberal Abdoulaye Wade, as he did again in 1988.

[9] He was Special Advisor for Energy and Mines to President Abdoulaye Wade from 6 April 2000 to 12 May 2003, as well as Director-General of the Petroleum Company of Senegal (Société des Pétroles du Sénégal, PETROSEN) from 13 December 2000 to 5 July 2001.

During his tenure he set in motion several presidential policies which had been started by his predecessor, including the Corniche de Dakar motorway and the construction of the Blaise Diagne International Airport.

[18] This was perceived as an attempt by Sall to weaken Karim's position and possibly influence the eventual presidential succession in favor of himself, provoking the enmity of Wade and his loyalists within the PDS.

He employed Jean-Pierre Pierre-Bloch [fr], a former member of the French National Assembly who had previously been a close associate of Wade, as an advisor.

[9] In the 2012 Presidential elections, Sall ran as the candidate of the "Macky 2012" coalition,[29] with the slogan, "The Path of Real Development" ("Yoonu Yookuté" in Wolof).

He campaigned across the country, without cutting off ties with the "23 Juin" (M23) opposition movement, which protested against Wade in Dakar calling for him to be barred from running for a third term.

[35] In the lead-up to the legislative elections in July 2012, for which he managed to preserve the Benno Bokk Yakaar coalition intact, Sall carried out many symbolic gestures.

In accordance with his promise to reduce state spending, he curtailed some ministerial perks, announced an audit of his predecessor's administration and cancelled 59 projects and agencies which were judged unnecessary.

Retirement pensions were revalued, farmers received emergency subsidies, and the 29 permits issued to foreign deep sea trawlers by the preceding government were annulled.

[35] Two difficult legal cases challenged his commitment to avoid interfering with the judiciary: the socialist Barthélémy Dias was charged with the murder of a PDS member and the marabout Béthio Thioune [fr], an old supporter of Wade was accused of being involved in the deaths of two of his followers.

While the World Trade Organisation called Sall's plans "ambitious," popular dissatisfaction with the slow pace of progress was reported.

On 1 May 2014, one of the leaders of the MFDC, Salif Sadio, sued for peace and declared a unilateral cease-fire after secret talks held at the Vatican between his forces and Sall.

[50] Sall told Putin he should be "aware that our countries, even if they are far from the theatre [of action], are victims of this economic crisis" caused by the Russian invasion of Ukraine.

[51] Sall also complained that the side effects of the EU's decision to expel many Russian banks from SWIFT will hurt the ability of African countries to pay for imported food and fertilizers from Russia.

[54] On 9 February 2023, the Sall announced his ambition to make Thiès the "city of three stations", with the prospect of its service by train Regional Express (TER) whose railway line will be extended to link it to Dakar.

[58][59] On 4 February, police in Dakar fired tear gas to disperse demonstrators protesting against the postponement and arrested Aminata Touré and candidate Anta Babacar Ngom,[60] who had attended one of the rallies after all 19 opposition candidates called for supporters to gather in the streets, including at a major roundabout and in front of the National Assembly.

Authorities also suspended and later revoked the broadcasting license of the private television channel Walf TV for its coverage of the protests, calling it an "incitement to violence".

[65] The Ministry of Communication, Telecommunications and Digital Economy shut off mobile internet access on 5 February, citing "the dissemination of several hateful and subversive messages relayed on social networks in the context of threats and disturbances to public order.

[70] In a televised interview on 22 February, Sall said that he would leave office as scheduled on 2 April, but said that he would hold talks first with political leaders to determine a new timetable for the elections.

[76] The election was won by opposition candidate Bassirou Diomaye Faye, and Sall left office at the end of his term on 2 April.

[77] Sall was named as the leading candidate of the opposition Takku Wallu Senegal coalition in the 2024 Senegalese parliamentary election scheduled on 17 November.

[91] Senegalese opposition leader Ousmane Sonko was arrested again in July 2023, with his political party being dissolved by the Ministry of Interior and Public Security.

[95] President Sall was awarded the 2020 Sunhak Peace Prize for successfully shortening the presidential term from seven to five years and reviving the economy through transparent policies.

He resigned from the position after leaving the presidency in October 2024, citing conflict of interest with his candidacy in upcoming parliamentary elections.