Relatives of those killed and the more than 160 people have long criticised the authorities' delay in holding a service.
The service, at St Philip's Cathedral in Birmingham, included the unveiling of the first memorial in the city to the bombings at the Mulberry Bush and Tavern pubs, 200 yards apart in the city centre, on 21 November 1974.
A crowd about 200 relatives and friends filled the church for the service led jointly by the Bishop of Aston, the Rt Rev John Austin, the assistant bishop, the Rt Rev Terence Brain, and the Birmingham president of the United Reformed Church, the Rev Irene Band.
Many wept as the names of the 21 killed were read. During the service relatives followed the ministers out in procession to the churchyard of the cathedral, where the memorial plaque was unveiled by Jim Eames, who was Lord Mayor of Birmingham at the time of the bombings.
Most relatives have laid wreaths alone outside the two pubs every year on the anniversary of the explosions.
Paul Beasley, 60, whose 30-year-old brother, Michael, was killed at the Mulberry Bush pub, has been to the site every year since the blast and promises he will return each year. Mr Beasley, from Acocks Green in Birmingham, said: "Today is a sad day. Sad for many reasons; that it has taken 21 years to get this service, and sad that the people who perpetrated this crime have never been brought to justice. It is terrible 21 innocent people lost their lives that night."