Shortly after graduating from college, Ma’ruf carried out dakwah missions in Jakarta. At that time, NU was still an active political party and Ma’ruf was elected to the Indonesian parliament, the People’s Representative Council (or DPR, Dewan Perwakilan Rakyat) in the national election held in 1971. Six years later, in 1977, he was elected to the Jakarta City Council as a member of the United Development Party (Partai Persatuan Pembangunan or PPP) for one term (1977–1982) and served as leader of the PPP caucus. At the end of his term, Ma’ruf returned to academia and social activism. In 1989, he was appointed as a katib ‘aam, a senior position within NU’s syuriah, its supreme governing council. He then rose to be one of the rais, a leader, overseeing the executive leadership of Abdurrahman Wahid.

Following the fall of Suharto in 1998, Ma’ruf became an advisor to Wahid’s National Awakening Party (Partai Kebangkitan Bangsa, or PKB) and advised Wahid throughout the period of his presidency of Indonesia from 1999 to 2001. Ma’ruf returned to active politics and represented the PKB in the national DPR from 1999 to 2004. During this second term in the DPR, Ma’ruf was chair of the Fourth Commission (agriculture, food, and maritime affairs) as well as member of the Second Commission (government affairs and regional autonomy) and Budgetary Board.

While a member of the DPR during 1999–2004, Ma’ruf chaired the Ulema Council’s committee in charge of issuing legal opinions (fatwa). He did not seek re-election to the DPR in 2004 and returned to the Indonesian Ulema Council (MUI) to chair its National Sharia Committee (acting from 2004 to 2010). He also served as an advisor to President Susilo Bambang Yudhoyono in his Presidential Advisory Council from 2007 to 2014.

In 2012, Ma’ruf also issued a recommendation that Muslims not say Merry Christmas, citing the controversy associated with the saying. However, in 2018, he noted that there was never an explicit ban of saying Christmas greetings issued by MUI, after a video of him saying Merry Christmas circulated.

Ma’ruf’s first wife, Siti Churiyah, died on 22 October 2013 at the age of 67. From the 49-year marriage, they had nine children and 13 grandchildren. Seven months later, on 31 May 2014, he married Wury Estu Handayani who had been a widow for around two years. They were married in a private ceremony at the well-known Sunda Kelapa Mosque in Menteng, Central Jakarta.

In 2015 Ma’ruf ran for the position of rais ‘aam syuriah of the NU, equivalent to chair of the supreme governing council. He finished in second place after the incumbent Ahmad Mustofa Bisri from Rembang’s Pesantren Raudlatuth Thalibin. In a significant development, Bisri withdrew his name from the race and Ma’ruf was then elected to the position by NU’s 33rd Congress.

Several weeks after his ascendancy to NU’s highest post, Ma’ruf was elected to be the chair of MUI, succeeding Muhammadiyah’s Din Syamsuddin on 27 August 2015.

As MUI chair, Ma’ruf gave his support to regulations prohibiting pornography and supported a decree banning Ahmadiya activities. In addition, Ma’ruf “regretted” the Constitutional Court’s ruling to reject a proposed ban on sexual activities of homosexuals in 2017, instead wanting “stern regulations”.

Ma’ruf was embroiled in part of the controversy surrounding the contentious Jakarta gubernatorial election in 2017. The then-Jakarta governor Basuki Tjahaja Purnama, widely known as “Ahok”, became the target of numerous protests in Jakarta in November 2016. In response, Ahok alleged that Ma’ruf had taken sides in the election due to a phone call with former president Susilo Bambang Yudhoyono, whose son Agus Harimurti Yudhoyono was running against Ahok in the election. Ahok later apologized to Ma’ruf via social media for any implication that Ma’ruf had been influenced by political pressure.

President Joko Widodo announced that he would run for re-election in the 2019 presidential election. His vice president Jusuf Kalla was not seen as eligible for another term because of the term limits set for the positions of president and vice-president. (Jusuf Kalla had already served a five-year term as vice-president Yudhoyono from 2004 to 2009.) Speculation as to who Jokowi might select as his running mate focused on several candidates including Mahfud MD, a former defence minister and chief justice of the Constitutional Court.

The General Elections Commission announced Widodo and Ma’ruf’s victory, with the pair securing 55.5 percent of the votes, on 21 May 2019, though Ma’ruf’s status as Vice President-elect was pending any lawsuits to the Constitutional Court.

Ma’ruf was sworn in as vice president on 20 October 2019. Aged 76 years and 223 days when inaugurated, he is the oldest-ever Indonesian vice president to be sworn in.

Ma’ruf is a fan of association football. He previously supported Manchester United, but after a few years of poor performances by the club, Ma’ruf switched his allegiance to its archrival Liverpool in 2019.