Two other cabinet ministers had only just been cleared by the corruption watchdog in June, ending what was labelled the "Ridout Road Saga".
The pair were accused of misusing their positions to secure premium state-owned property at below market rates.
Meanwhile on the other side of the political divide, the opposition Workers' Party (WP) also lost two senior members, who also admitted last month to an inappropriate relationship despite earlier denials.
The WP said MP Leon Perera and youth wing president Nicole Seah handed in letters of resignation after a video circulated on social media showing them holding hands.
The flurry of misconduct is surprising because government scandals are rare in Singapore.
The repudiation of corruption has been a core principle since founding prime minister Lee Kuan Yew took office in 1959 dressed with his team in white and vowing that leaders must be "whiter than white".
Ministers are paid more than S$1 million ($1.13 million) a year to discourage corruption and attract the best and brightest.
The last criminal corruption investigation was in 1986 — the accused MP took his own life before he could be charged — and the most recent resignations of members of parliament were in 2012 and 2016.
Government's handling questioned
In the wake of the scandals, the ruling PAP's leaders have promised transparency.
Still, many Singaporeans have been poring over the details and raising questions on social media.
During a press conference, Mr Lee said he knew about the relationship between the two parliamentarians in 2020, leaving many wondering why they were stepping down now.
He last week admitted he "should have forced the issue earlier".
Questions have also been raised about why it took a number of days for it to be revealed that Mr Iswaran had been arrested.