The Unite for Freedom rally saw huge crowds marching and shouting demands for “medical freedom”.
Signs saying “freedom is non-negotiable” were held up as people let off brightly coloured smoke flares.
Activists also carried giant inflatable syringes to protest what they called “coerced vaccinations”.
The demonstrators were not wearing masks at the illegal gathering.
The protestors heckled shoppers wearing masks on Oxford Street as they moved through the sun drenched capital.
Actor Laurence Fox, who is standing for London Mayor with a manifesto stating his opposition to lockdowns, was at the protest.
He tweeted: “We stand together for freedom. What a beautiful day, with the best of people.”
Piers Corbyn, the brother of former Labour leader Jeremy, was also on the march. He has been a prominent figure in the anti-lockdown movement.
The demonstrators refused to observe any social distancing rules and many people stood shoulder to shoulder.
Organisers had urged participants to “make as much noise as possible” during the rally but to “avoid making a crowd”.
However, they also encouraged people to “link arms if the police tried to intervene”.
Their aim is to fight against all pandemic rules and use the slogan “no new normal” to reject moves to help fight the pandemic which puts restrictions on everyday life.
The Metropolitan Police said a 38-year-old man was arrested near Embankment on suspicion of a public order offence, while a 37-year-old man was arrested near Trafalgar Square on suspicion of being drunk and disorderly and a public order allegation.
The force said both men have been taken into custody as inquiries continue.
They said on Twitter: “We have a policing operation in central London today as a result of a number of demonstrations.
“Anyone coming into London for a protest must make sure their gathering is lawful, with a risk assessment carried out by the organiser.
“Officers are on site and are engaging with those taking part.”
The demonstrators were challenging lockdown measures, despite many being lifted earlier this month.
Pubs, restaurants and gyms reopened on April 12, along with zoos, theme parks and hairdressers.
Lockdown restrictions are set to ease further on May 17, allowing food and drink indoors.
If the government’s so-called road map is followed all restrictions should be lifted on June 21.
The Government is said to want Covid passports introduced by May 17, when foreign travel resumes, to allow holidaymakers to avoid quarantine.
But Britain’s equalities watchdog has warned such measures could be unlawful and create a “two-tier society” which discriminates against the poor, migrants and ethnic minorities.
Half of Britons, more than 33.4 million, have now received a first Covid jab.