Tinubu's joined the Social Democratic Party. In 1992, he was elected to the Senate, representing the Lagos West constituency in the short-lived Nigerian Third Republic

After the results of the 12 June 1993 presidential elections were annulled, Tinubu became a founding member of the pro-democracy National Democratic Coalition, a group which mobilized support for the restoration of democracy and recognition of Moshood Abiola as winner of the 12 June election. Following the seizure of power as military head of state of General Sani Abacha, he went into exile in 1994 and returned to the country in 1998 after the death of the military dictator, which ushered in the transition to the Fourth Nigerian Republic.

In the run-up to the 1999 elections, Bola Tinubu was a protégé of Alliance for Democracy (AD) leaders Abraham Adesanya and Ayo Adebanjo. He went on to win the AD primaries for the Lagos State governorship elections in defeating Funsho Williams and Wahab Dosunmu, a former Minister of Works and Housing. In January 1999, he stood for the position of Governor of Lagos State on the AD ticket and was elected governor.

In February 2013, Tinubu was among several politicians who created a "mega opposition" party with the merger of Nigeria's three biggest opposition parties – the Action Congress of Nigeria (ACN), the Congress for Progressive Change (CPC), the All Nigeria Peoples Party (ANPP), a faction of the All Progressives Grand Alliance (APGA) and the new PDP (nPDP), a faction of the then ruling People's Democratic Party[22] – into the All Progressives Congress (APC).

In 2014, Tinubu supported former military head of state General Muhammadu Buhari, leader of the CPC faction of the APC – who commanded widespread following in Northern Nigeria, and had previously contested in the 2003, 2007 and 2011 presidential elections as the CPC presidential candidate.

On 10 January 2022, Tinubu made his formal announcement of candidacy for president.

On 8 June 2022, Tinubu won the party convention vote of the ruling APC, scoring 1,271, to defeat Vice President Yemi Osinbajo and Rotimi Amaechi who scored 235 and 316 respectively.

On 1 March 2023, INEC declared Tinubu winner of the 2023 presidential election. He was declared president-elect after he polled 8,794,726 votes to defeat his opponents. His runner-up Atiku Abubakar of the opposition People's Democratic Party (PDP) polled 6,984,520 votes. Labour Party's Peter Obi had 6,101,533 votes to come third.

Tinubu married Oluremi Tinubu, in 1987. They have 3 children, Zainab Abisola Tinubu, Habibat Tinubu and Olayinka Tinubu.

He fathered 3 children from previous relationships, Late Kazeem Olajide Tinubu Folashade Tinubu and Oluwaseyi Tinubu.

Tinubu's mother, Abibatu Mogaji, died on 15 June 2013 at the age of 96. On 31 October 2017, his son, Jide Tinubu, died in London.

Tinubu is a Muslim.

Tinubu holds two chieftaincies; he is the "Asiwaju" of Lagos and the "Jagaban" of the Borgu Emirate in Niger State.