The men, aged 48 and 30, were arrested under anti-terrorism legislation in Newport in Wales, police said in a statement, after a 25-year-old man was arrested in the same city on Tuesday.
"This continues to be a fast-moving investigation," Dean Haydon, head of counter-terrorism at London's Metropolitan Police, said in the statement.
"We now have five men in custody and searches are continuing at four addresses," he said.
"We anticipate that the searches will take some days to complete and may cause further disruption".
Friday's attack on a train at Parsons Green station in west London was claimed by the Daesh group.
A bomb hidden in a large white bucket apparently failed to detonate fully when it went off during morning rush hour but instead released what witnesses described as a "fireball" into the air.
Some commuters suffered burns, while others were injured in the stampede to the exit that ensued.
The bombing was the fifth terror attack in Britain in six months, which combined have claimed 35 lives.
The terror alert in Britain was raised to its maximum "critical" level on Friday, meaning another attack was believed to be imminent. It was lowered back to "severe" on Sunday.
An 18-year-old man, reportedly an Iraqi refugee, was arrested in the ferry departure terminal of the port of Dover on Saturday and a 21-year-old man was detained later the same day in west London.
The 21-year-old was named by British media, who said he was originally from Syria and had been working at a fast food chicken restaurant.
The police investigation has focused on a foster home in Sunbury-on-Thames, a suburb of London where the 18-year-old is believed to have lived.
Police said searches were also continuing at another address near London and two properties in Newport.