While 15 countries have legalised gay marriage and in another three it is allowed in some regions of the country, homosexuals remain persecuted in many parts of the world.
The Church of England, insisting weddings should take place only between a man and a woman, secured an exemption from the new law.
In London, John Coffey, 52, and Bernardo Marti, 48, exchanged vows as the clock struck midnight, before being pronounced "husband and husband".
They were among several couples bidding to be first to take advantage of the Marriage (Same Sex Couples) Act.
In Brighton on England's south coast, Neil Allard and Andrew Wale exchanged vows and rings in the opulent splendour of the Royal Pavilion in front of about 100 guests.
Wearing velvet-collared three-piece suits with white flowers in the buttonholes, the smiling couple of seven years hugged and kissed after sealing their marriage.
"We are very happy this day has come finally. It's very exciting," said Wale, a 49-year-old theatre director.
Campaigners have insisted that only the right to marry gives them full equality with heterosexual couples.
"These weddings will send a powerful signal to every young person growing up to be lesbian, gay or bisexual -- you can be who you are and love who you love, regardless of your sexual orientation," said Ruth Hunt, acting chief executive for gay rights charity Stonewall.
Civil partnerships in England have been legal since 2005 and marriage brings no new rights -- the ability to adopt, for example, was introduced in 2002.
"We didn't want to get married until it was a marriage that my mum and dad could have," said Teresa Millward, 37, who was marrying her long-term girlfriend on Saturday.
The gay marriage law is the final victory in a long battle stretching back to the decriminalisation of homosexuality in England in 1967.
Cameron backed the change despite strong opposition from members of his party and the Church of England, which has rejected the idea that clergy be allowed to bless couples in same-sex marriages.
But Archbishop of Canterbury Justin Welby, the leader of the world's 80 million Anglicans, indicated on Thursday that the Church would no longer campaign against the issue, and would continue to demonstrate "the love of Christ for every human being".
- Resistance elsewhere -
A poll for BBC radio said 20 percent of British adults would turn down an invitation to a same-sex wedding.
However, the survey also found 68 percent agreed gay marriage should be permitted, with 26 percent opposing it.
Peter McGraith and David Cabreza, who have been together for 17 years, also married shortly after midnight in front of friends and their two adopted sons in London.
They hope their wedding will send out a message to places like Nigeria, Uganda and Russia where the idea of gay marriage is a distant dream.
"There's a lot of gay men and lesbians around the world who are not invited to the party," McGraith, a clothing designer, told AFP ahead of the big day.
Same-sex couples who were married abroad are now recognised under the new law, although not everywhere in the United Kingdom.
Scotland, which has devolved powers, is expected to introduce gay marriage later this year, while the British-controlled province of Northern Ireland remains deeply divided on the issue and has no plans to change the law there.